Precedex
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Precedex
SIDE EFFECTS
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 (dexmedetomidine hydrochloride) 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 (dexmedetomidine hydrochloride) for sedation in the Intensive Care Unit setting in which 1007 patients received Precedex (dexmedetomidine hydrochloride) . 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%— Intensive
Care Unit Sedation Population < 24 hours*
| Adverse Event | All Precedex (dexmedetomidine hydrochloride) (N=1007) (%) |
Randomized Precedex (dexmedetomidine hydrochloride) (N=798)(%) |
Placebo (N=400) (%) |
Propofol (N=188) (%) |
| Hypotension | 25% | 24% | 12% | 13% |
| Hypertension | 12% | 13% | 19% | 4% |
| Nausea | 9% | 9% | 9% | 11% |
| Bradycardia | 5% | 5% | 3% | 0 |
| Atrial fibrillation | 4% | 5% | 3% | 7% |
| Pyrexia | 4% | 4% | 4% | 4% |
| Dry mouth | 4% | 3% | 1% | 1% |
| Vomiting | 3% | 3% | 5% | 3% |
| Hypovolemia | 3% | 3% | 2% | 5% |
| Atelectasis | 3% | 3% | 3% | 6% |
| Pleural effusion | 2% | 2% | 1% | 6% |
| Agitation | 2% | 2% | 3% | 1% |
| Tachycardia | 2% | 2% | 4% | 1% |
| Anemia | 2% | 2% | 2% | 2% |
| Hyperthermia | 2% | 2% | 3% | 0 |
| Chills | 2% | 2% | 3% | 2% |
| Hyperglycemia | 2% | 2% | 2% | 3% |
| Hypoxia | 2% | 2% | 2% | 3% |
| Post-procedural hemorrhage | 2% | 2% | 3% | 4% |
| Pulmonary edema | 1% | 1% | 1% | 3% |
| Hypocalcemia | 1% | 1% | 0 | 2% |
| Acidosis | 1% | 1% | 1% | 2% |
| Urine output decreased | 1% | 1% | 0 | 2% |
| Sinus tachycardia | 1% | 1% | 1% | 2% |
| Ventricular tachycardia | <1% | 1% | 1% | 5% |
| Wheezing | <1% | 1% | 0 | 2% |
| 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 (dexmedetomidine hydrochloride) for sedation in the surgical intensive care unit setting in which 387 patients received Precedex (dexmedetomidine hydrochloride) 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 Patients in the Randomized Placebo-controlled
Continuous Infusion < 24 Hours ICU Sedation Studies
| Adverse Event | Randomized Dexmedetomidine (N=387) |
Placebo (N=379) |
| Hypotension | 28% | 13% |
| Hypertension | 16% | 18% |
| Nausea | 11% | 9% |
| Bradycardia | 7% | 3% |
| Fever | 5% | 4% |
| Vomiting | 4% | 6% |
| Atrial Fibrillation | 4% | 3% |
| Hypoxia | 4% | 4% |
| Tachycardia | 3% | 5% |
| Hemorrhage | 3% | 4% |
| Anemia | 3% | 2% |
| Dry Mouth | 3% | 1% |
| Rigors | 2% | 3% |
| Agitation | 2% | 3% |
| Hyperpyrexia | 2% | 3% |
| Pain | 2% | 2% |
| Hyperglycemia | 2% | 2% |
| Acidosis | 2% | 2% |
| Pleural Effusion | 2% | 1% |
| Oliguria | 2% | < 1% |
| Thirst | 2% | < 1% |
In a controlled clinical trial, Precedex (dexmedetomidine hydrochloride) was compared to midazolam for ICU sedation exceeding 24 hours duration. 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 (dexmedetomidine hydrochloride) group is provided in Table 5.
Table 4: 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 *
| Adverse Event | Dexmedetomidine (N=244) |
Midazolam (N=122) |
| Hypotension1 | 56% | 56% |
| Hypotension requiring intervention | 28% | 27% |
| Bradycardia2 | 42% | 19% |
| Bradycardia requiring intervention | 5% | 1% |
| Systolic Hypertension3 | 28% | 42% |
| Tachycardia4 | 25% | 44% |
| Tachycardia requiring intervention | 10% | 10% |
| Diastolic Hypertension3 | 12% | 15% |
| Hypertension3 | 11% | 15% |
| Hypertension requiring intervention † | 19% | 30% |
| Hypokalemia | 9% | 13% |
| Pyrexia | 7% | 2% |
| Agitation | 7% | 6% |
| Hyperglycemia | 7% | 2% |
| Constipation | 6% | 6% |
| Hypoglycemia | 5% | 6% |
| Respiratory Failure | 5% | 3% |
| Renal Failure Acute | 2% | 1% |
| Acute Respiratory Distress Syndrome | 2% | 1% |
| Generalized edema | 2% | 6% |
| Hypomagnesemia | 1% | 7% |
| †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. |
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The following adverse events occurred between 2 and 5% for Precedex (dexmedetomidine hydrochloride) 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 subjects who had a dose-related increase
in Treatment Emergent Adverse Events by maintenance adjusted dose rate range
in the Precedex (dexmedetomidine hydrochloride) group Precedex (dexmedetomidine hydrochloride) mcg/kg/hr
| Adverse Event | Precedex mcg/kg/hr | ||
| ≤ 0.7* N = 95 |
> 0.7 to ≤ 1.1* N = 78 |
> 1.1* N = 71 |
|
| Constipation | 6% | 5% | 14% |
| Agitation | 5% | 8% | 14% |
| Anxiety | 5% | 5% | 9% |
| Oedema peripheral | 3% | 5% | 7% |
| Atrial fibrillation | 2% | 4% | 9% |
| Respiratory failure | 2% | 6% | 10% |
| Acute respiratory distress syndrome | 1% | 3% | 9% |
| *Average maintenance dose over the entire study drug administration | |||
Procedural Sedation
Adverse reaction information is derived from the two trials for procedural sedation in which 318 patients received Precedex (dexmedetomidine hydrochloride) . 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, 30% ≥ 65 years of age, 52% male and 61%
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]. Prespecified 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 (dexmedetomidine hydrochloride) and comparator groups in both studies.
Table 6: Adverse Reactions With an Incidence > 2%— Procedural
Sedation Population
| Adverse Event | Precedex (dexmedetomidine hydrochloride) N = 318 (%) |
Placebo N = 113 (%) |
| Hypotension1 | 54% | 30% |
| Respiratory depression2 | 37% | 32% |
| Bradycardia3 | 14% | 4% |
| Hypertension4 | 13% | 24% |
| Tachycardia5 | 5% | 17% |
| Nausea | 3% | 2% |
| Dry mouth | 3% | 1% |
| Hypoxia6 | 2% | 3% |
| Bradypnea | 2% | 4% |
| 1 Hypotension was defined in absolute
and relative terms as Systolic blood pressure of < 80 mmHg or ≤ 30%
lower than pre-study 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 pre-study 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 |
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Postmarketing Experience
The following adverse reactions have been identified during post approval use of Precedex (dexmedetomidine hydrochloride) . 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 (dexmedetomidine hydrochloride) during post approval use of the drug.
Table 7: Adverse Reactions Experienced During Post-approval
Use of Precedex (dexmedetomidine hydrochloride)
| Body System | Preferred Term |
| Body as a Whole | Fever, hyperpyrexia, hypovolemia, light anesthesia, pain, rigors |
| Cardiovascular Disorders, General | Blood pressure fluctuation, heart disorder, hypertension, hypotension, myocardial infarction |
| Central and Peripheral Nervous System Disorders | Dizziness, headache, neuralgia, neuritis, speech disorder, convulsion |
| Gastrointestinal System Disorders | Abdominal pain, diarrhea, vomiting, nausea |
| Heart Rate and Rhythm Disorders | Arrhythmia, ventricular arrhythmia, bradycardia, hypoxia, atrioventricular block, cardiac arrest, extrasystoles, atrial fibrillation, heart block, t wave inversion, tachycardia, supraventricular tachycardia, ventricular tachycardia |
| Liver and Biliary System Disorders | Increased gamma-glutamyl transpepsidase, hepatic function abnormal, hyperbilirubinemia, alanine transaminase, aspartate aminotransferase |
| Metabolic and Nutritional Disorders | Acidosis, respiratory acidosis, hyperkalemia, increased alkaline phosphatase, thirst, hypoglycemia |
| Psychiatric Disorders | Agitation, confusion, delirium, hallucination, illusion |
| Red Blood Cell Disorders | Anemia |
| Renal disorders | Blood urea nitrogen increased, oliguria |
| Respiratory System Disorders | Apnea, bronchospasm, dyspnea, hypercapnia, hypoventilation, hypoxia, pulmonary congestion |
| Skin and Appendages Disorders | Increased sweating |
| Vascular disorders | Hemorrhage |
| Vision Disorders | Photopsia, abnormal vision |
Read the Precedex (dexmedetomidine hydrochloride) Side Effects Center for a complete guide to possible side effects »
DRUG INTERACTIONS
Anesthetics, Sedatives, Hypnotics, Opioids
Co-administration of Precedex (dexmedetomidine hydrochloride) 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 (dexmedetomidine hydrochloride) and isoflurane, propofol, alfentanil and midazolam have been demonstrated. However, due to possible pharmacodynamic interactions, when co-administered with Precedex (dexmedetomidine hydrochloride) , a reduction in dosage of Precedex (dexmedetomidine hydrochloride) or the concomitant anesthetic, sedative, hypnotic or opioid may be required.
Neuromuscular Blockers
In one study of 10 healthy volunteers, administration of Precedex (dexmedetomidine hydrochloride) 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.
Drug Abuse And Dependence
Controlled Substance
Precedex (dexmedetomidine hydrochloride) is not a controlled substance.
Dependence
The dependence potential of Precedex (dexmedetomidine hydrochloride) has not been studied in humans. However, since studies in rodents and primates have demonstrated that Precedex (dexmedetomidine hydrochloride) exhibits pharmacologic actions similar to those of clonidine, it is possible that Precedex (dexmedetomidine hydrochloride) may produce a clonidine-like withdrawal syndrome upon abrupt discontinuation [see WARNINGS AND PRECAUTIONS].
Last reviewed on RxList: 11/15/2010
This monograph has been modified to include the generic and brand name in many instances.
Additional Precedex Information
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