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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]
- Transient hypertension [see WARNINGS AND PRECAUTIONS]
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 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 2. The most frequent adverse reactions were hypotension, bradycardia and dry mouth [see WARNINGS AND PRECAUTIONS].
Table 2: Adverse Reactions with an Incidence > 2%—Adult
Intensive Care Unit Sedation Population < 24 hours*
|Adverse Event||All Precedex
(N = 1007)
(N = 798)
(N = 400)
(N = 188)
|Urine Output Decreased||1%||1%||0||2%|
|Ventricular Tachycardia||< 1%||1%||1%||5%|
|Edema Peripheral||< 1%||0||1%||2%|
|* 26 subjects in the all Precedex group and 10 subjects in the randomized Precedex group had exposure for greater than 24 hours.|
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 3).
Table 3: Treatment-Emergent Adverse Events Occurring
in > 1% Of All Dexmedetomidine-Treated Adult Patients in the Randomized
Placebo-Controlled Continuous Infusion < 24 Hours ICU Sedation Studies
|Adverse Event||Randomized Dexmedetomidine
(N = 387)
(N = 379)
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 patients in the randomized active comparator continuous infusion long-term intensive care unit sedation study are provided in Table 4. The number (%) of 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 5.
Table 4: 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
(N = 244)
(N = 122)
|Hypotension Requiring Intervention||28%||27%|
|Bradycardia Requiring Intervention||5%||1%|
|Tachycardia Requiring Intervention||10%||10%|
|Hypertension Requiring Intervention†||19%||30%|
|Renal Failure Acute||2%||1%|
|Acute Respiratory Distress Syndrome||2%||1%|
|† Includes any type of hypertension.
1 Hypotension was defined in absolute terms as Systolic blood pressure of < 80 mmHg or Diastolic blood pressure of < 50 mmHg or in relative terms as ≤ 30% lower than pre-study drug infusion value.
2 Bradycardia was defined in absolute terms as < 40 bpm or in relative terms as ≤ 30% lower than pre-study drug infusion value.
3 Hypertension was defined in absolute terms as Systolic blood pressure > 180 mmHg or Diastolic blood pressure of > 100 mmHg or in relative terms as ≥ 30% higher than pre-study drug infusion value.
4 Tachycardia was defined in absolute terms as > 120 bpm or in relative terms as ≥ 30% greater than pre-study drug infusion value.
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%).
Table 5: 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
|Adverse Event||Precedex mcg/kg/hr|
| ≤ 0.7*
(N = 95)
| > 0.7 to ≤ 1.1*
(N = 78)
| > 1.1*
(N = 71)
|Acute Respiratory Distress Syndrome||1%||3%||9%|
|* Average maintenance dose over the entire study drug administration|
Adverse reaction information is derived from the two trials for procedural sedation [see Clinical Studies] 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 at an incidence of > 2% are provided in Table 6. The most frequent adverse reactions were hypotension, bradycardia, and dry mouth [see WARNINGS AND PRECAUTIONS]. 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.
Table 6: Adverse Reactions With an Incidence > 2%—Procedural
(N = 318)
(N = 113)
|1 Hypotension was defined in absolute and relative terms
as Systolic blood pressure of < 80 mmHg or ≤ 30% lower than prestudy drug
infusion value, or Diastolic blood pressure of < 50 mmHg.
2 Respiratory depression was defined in absolute and relative terms as respiratory rate (RR) < 8 beats per minute or > 25% decrease from baseline.
3 Bradycardia was defined in absolute and relative terms as < 40 beats per minute or ≤ 30% lower than pre-study drug infusion value.
4 Hypertension was defined in absolute and relative terms as Systolic blood pressure > 180 mmHg or ≥ 30% higher than prestudy drug infusion value or Diastolic blood pressure of > 100 mmHg.
5 Tachycardia was defined in absolute and relative terms as > 120 beats per minute or ≥ 30% greater than pre-study drug infusion value.
6 Hypoxia was defined in absolute and relative terms as SpO2 < 90% or 10% decrease from baseline.
The following adverse reactions have been identified during post approval use of Precedex. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Hypotension and bradycardia were the most common adverse reactions associated with the use of Precedex during post approval use of the drug.
Table 7: Adverse Reactions Experienced During
Post-approval Use of Precedex
|System Organ Class||Preferred Term|
|Blood and Lymphatic System Disorders||Anemia|
|Cardiac Disorders||Arrhythmia, atrial fibrillation, atrioventricular block, bradycardia, cardiac arrest, cardiac disorder, extrasystoles, myocardial infarction, supraventricular tachycardia, tachycardia, ventricular arrhythmia, ventricular tachycardia|
|Eye Disorders||Photopsia, visual impairment|
|Gastrointestinal Disorders||Abdominal pain, diarrhea, nausea, vomiting|
|General Disorders and Administration Site Conditions||Chills, hyperpyrexia, pain, pyrexia, thirst|
|Hepatobiliary Disorders||Hepatic function abnormal, hyperbilirubinemia|
|Investigations||Alanine aminotransferase increased, aspartate aminotransferase increased, blood alkaline phosphatase increased, blood urea increased, electrocardiogram T wave inversion, gammaglutamyltransferase increased|
|Metabolism and Nutrition Disorders||Acidosis, hyperkalemia, hypoglycemia, hypovolemia|
|Nervous System Disorders||Convulsion, dizziness, headache, neuralgia, neuritis, speech disorder|
|Psychiatric Disorders||Agitation, confusional state, delirium, hallucination, illusion|
|Renal and Urinary Disorders||Oliguria, polyuria|
|Respiratory, Thoracic and Mediastinal Disorders||Apnea, bronchospasm, dyspnea, hypercapnia, hypoventilation, hypoxia, pulmonary congestion, respiratory acidosis|
|Skin and Subcutaneous Tissue Disorders||Hyperhidrosis|
|Surgical and Medical Procedures||Light anesthesia|
|Vascular Disorders||Blood pressure fluctuation, hemorrhage, hypertension, hypotension|
Read the Precedex (dexmedetomidine hydrochloride) Side Effects Center for a complete guide to possible side effects
Anesthetics, Sedatives, Hypnotics, Opioids
Co-administration of Precedex with anesthetics, sedatives, hypnotics, and opioids is likely to lead to an enhancement of effects. Specific studies have confirmed these effects with sevoflurane, isoflurane, propofol, alfentanil, and midazolam. No pharmacokinetic interactions between Precedex and isoflurane, propofol, alfentanil and midazolam have been demonstrated. However, due to possible pharmacodynamic interactions, when co-administered with Precedex, a reduction in dosage of Precedex or the concomitant anesthetic, sedative, hypnotic or opioid may be required.
In one study of 10 healthy adult volunteers, administration of Precedex for 45 minutes at a plasma concentration of one ng/mL resulted in no clinically meaningful increases in the magnitude of neuromuscular blockade associated with rocuronium administration.
In vitro studies suggested that Precedex is metabolized by several cytochrome P450 enzymes CYP2A6, CYP1A2, CYP2E1, CYP2D6 and CYP2C19 with no apparent predominant pathways. Precedex has shown strongest properties for inhibition of CYP2D6, CYP3A4 and CYP2B6. Use caution during concomitant administration of Precedex with other medicines metabolized by CYP2D6, CYP3A4 and CYP2B6 enzymes.
Drug Abuse And Dependence
Precedex (dexmedetomidine hydrochloride) is not a controlled substance.
The dependence potential of Precedex has not been studied in humans. However, since studies in rodents and primates have demonstrated that Precedex exhibits pharmacologic actions similar to those of clonidine, it is possible that Precedex may produce a clonidine-like withdrawal syndrome upon abrupt discontinuation [see WARNINGS AND PRECAUTIONS].This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 5/2/2016
Additional Precedex Information
Report Problems to the Food and Drug Administration
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