Other hypnotics and sedatives

Dexmedetomidine Hydrochloride

Approved 20 Aug 2015InjectionInjectable

The FDA lists this product in 58 strengths and forms.

Indications

Dexmedetomidine hydrochloride injection is a relatively selective alpha 2 -adrenergic agonist indicated for:

Sedation of non-intubated patients prior to and/or during surgical and other procedures. (1.2)

1.2Procedural Sedation

Dexmedetomidine hydrochloride injection is indicated for sedation of non-intubated patients prior to and/or during surgical and other procedures.

Contraindications

None None. ( 4 )

Warnings and precautions

Monitoring: Continuously monitor patients while receiving dexmedetomidine hydrochloride. ( 5.1 )
Bradycardia and Sinus Arrest: Have occurred in young healthy volunteers with high vagal tone or with different routes of administration, e.g., rapid intravenous or bolus administration. ( 5.2 )
Hypotension and Bradycardia: May necessitate medical intervention. May be more pronounced in patients with hypovolemia, diabetes mellitus, or chronic hypertension, and in the elderly. Use with caution in patients with advanced heart block or severe ventricular dysfunction. ( 5.2 )
Co-administration with Other Vasodilators or Negative Chronotropic agents: Use with caution due to additive pharmacodynamic effects. ( 5.2 )
Transient Hypertension: Observed primarily during the loading dose. Consider reduction in loading infusion rate. ( 5.3 )
Arousability: Patients can become aroused/alert with stimulation; this alone should not be considered as lack of efficacy ( 5.4 )
Prolonged exposure to dexmedetomidine beyond 24 hours may be associated with tolerance and tachyphylaxis and a dose-related increase in adverse events ( 5.6 )

5.1Drug Administration

Dexmedetomidine hydrochloride should be administered only by persons skilled in the management of patients in the operating room setting. Due to the known pharmacological effects of dexmedetomidine hydrochloride, patients should be continuously monitored while receiving dexmedetomidine hydrochloride.

Indications

Dexmedetomidine hydrochloride injection is a relatively selective alpha 2 -adrenergic agonist indicated for:

Sedation of non-intubated patients prior to and/or during surgical and other procedures. (1.2)

1.2Procedural Sedation

Dexmedetomidine hydrochloride injection is indicated for sedation of non-intubated patients prior to and/or during surgical and other procedures.

Warnings and precautions

Monitoring: Continuously monitor patients while receiving dexmedetomidine hydrochloride. ( 5.1 )
Bradycardia and Sinus Arrest: Have occurred in young healthy volunteers with high vagal tone or with different routes of administration, e.g., rapid intravenous or bolus administration. ( 5.2 )
Hypotension and Bradycardia: May necessitate medical intervention. May be more pronounced in patients with hypovolemia, diabetes mellitus, or chronic hypertension, and in the elderly. Use with caution in patients with advanced heart block or severe ventricular dysfunction. ( 5.2 )
Co-administration with Other Vasodilators or Negative Chronotropic agents: Use with caution due to additive pharmacodynamic effects. ( 5.2 )
Transient Hypertension: Observed primarily during the loading dose. Consider reduction in loading infusion rate. ( 5.3 )
Arousability: Patients can become aroused/alert with stimulation; this alone should not be considered as lack of efficacy ( 5.4 )
Prolonged exposure to dexmedetomidine beyond 24 hours may be associated with tolerance and tachyphylaxis and a dose-related increase in adverse events ( 5.6 )

5.1Drug Administration

Pregnancy and breastfeeding

8.1Pregnancy Pregnancy Category C:

There are no adequate and well-controlled studies of dexmedetomidine hydrochloride use in pregnant women. In an in vitro human placenta study, placental transfer of dexmedetomidine occurred. In a study in the pregnant rat, placental transfer of dexmedetomidine was observed when radiolabeled dexmedetomidine was administered subcutaneously. Thus, fetal exposure should be expected in humans, and dexmedetomidine hydrochloride should be used during pregnancy only if the potential benefits justify the potential risk to the fetus.

Teratogenic effects were not observed in rats following subcutaneous administration of dexmedetomidine during the period of fetal organogenesis (from gestation day 5 to 16) with doses up to 200 mcg/kg (representing a dose approximately equal to the maximum recommended human intravenous dose based on body surface area) or in rabbits following intravenous administration of dexmedetomidine during the period of fetal organogenesis (from gestation day 6 to 18) with doses up to 96 mcg/kg (representing approximately half the human exposure at the maximum recommended dose based on plasma area under the time-curve comparison).

However, fetal toxicity, as evidenced by increased post-implantation losses and reduced live pups, was observed in rats at a subcutaneous dose of 200 mcg/kg. The no-effect dose in rats was 20 mcg/kg (representing a dose less than the maximum recommended human intravenous dose based on a body surface area comparison). In another reproductive toxicity study when dexmedetomidine was administered subcutaneously to pregnant rats at 8 and 32 mcg/kg (representing a dose less than the maximum recommended human intravenous dose based on a body surface area comparison) from gestation day 16 through weaning, lower offspring weights were observed.

Additionally, when offspring of the 32 mcg/kg group were allowed to mate, elevated fetal and embryocidal toxicity and delayed motor development was observed in second generation offspring.

Adverse reactions

The most common adverse reactions (incidence greater than 2%) are hypotension, bradycardia, and dry mouth. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc. at 1-800-818-4555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

6.1Clinical 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 dexmedetomidine hydrochloride has been associated with the following serious adverse reactions:

Hypotension, bradycardia and sinus arrest [ see Warnings and Precautions (5.2) ]
Transient hypertension [ see Warnings and Precautions (5.3) ] Most common treatment-emergent adverse reactions, occurring in greater than 2% of patients in procedural sedation studies include hypotension, bradycardia and dry mouth. Procedural Sedation Adverse reaction information is derived from the two trials for procedural sedation [see Clinical Studies (14.2) ] in which 318 adult patients received 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, 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 (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 dexmedetomidine hydrochloride and comparator groups in both studies. Table 6: Adverse Reactions With an Incidence > 2% — Procedural Sedation Population Adverse Event Dexmedetomidine Hydrochloride N = 318 (%) Placebo N = 113 (%) Hypotension 1 54% 30% Respiratory depression 2 37% 32% Bradycardia 3 14% 4% Hypertension 4 13% 24% Tachycardia 5 5% 17% Nausea 3% 2% Dry mouth 3% 1% Hypoxia 6 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

6.2Postmarketing Experience

The following adverse reactions have been identified during post approval use of 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 dexmedetomidine hydrochloride during post approval use of the drug.

Table 7: Adverse Reactions Experienced During Post-approval Use of Dexmedetomidine Hydrochloride System Organ Class 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, electrocardiogram QT prolonged Metabolism and Nutrition Disorders Acidosis, hyperkalemia, hypoglycemia, hypovolemia, hypernatremia 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

Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA

Dexmedetomidine Hydrochloride

Indications

1.2Procedural Sedation

Contraindications

Warnings and precautions

5.1Drug Administration

Two medicines in one question?

Dexmedetomidine Hydrochloride

Indications

1.2Procedural Sedation

Contraindications

Warnings and precautions

5.1Drug Administration

Two medicines in one question?

5.2Hypotension, Bradycardia, and Sinus Arrest

5.3Transient Hypertension

5.4Arousability

5.5Withdrawal Procedural Sedation

5.6Tolerance and Tachyphylaxis Use

5.7Hepatic Impairment

Interactions

7.1Anesthetics, Sedatives, Hypnotics, Opioids Co-administration

7.2Neuromuscular Blockers

Pregnancy and breastfeeding

8.1Pregnancy Pregnancy Category C:

Adverse reactions

6.1Clinical Studies Experience

6.2Postmarketing Experience

Composition

Strengths and forms

Official product information

At a glance