Dexmedetomidine HCl Injection - Product Information
|Manufacture:||Fresenius Kabi USA, LLC|
|Class:||Miscellaneous anxiolytics, sedatives and hypnotics|
|Form:||Liquid solution, Intravenous (IV)|
Indications and Usage
Dexmedetomidine Hydrochloride Injection is indicated for sedation of non-intubated patients prior to and/or during surgical and other procedures.
Dosage and Administration
Dexmedetomidine Hydrochloride Injection dosing should be individualized and titrated to desired clinical response.
Dexmedetomidine Hydrochloride Injection is not indicated for infusions lasting longer than 24 hours.
Dexmedetomidine Hydrochloride Injection should be administered using a controlled infusion device.
|INDICATION||DOSAGE AND ADMINISTRATION|
|Initiation of Procedural Sedation||
For adult patients : a loading infusion of one mcg/kg over 10 minutes . For less invasive procedures such as ophthalmic surgery, a loading infusion of 0.5 mcg/kg given over 10 minutes may be suitable.
For patients over 65 years of age: a loading infusion of 0.5 mcg/kg over 10 minutes [see Use in Specific Populations].
For adult patients with impaired hepatic function: a dose reduction should be considered [see Use in Specific Populations , Clinical Pharmacology].
|Maintenance of Procedural Sedation||
For adult patients : the maintenance infusion is generally initiated at 0.6 mcg/kg/hour and titrated to achieve desired clinical effect with doses ranging from 0.2 to 1 mcg/kg/hour. The rate of the maintenance infusion should be adjusted to achieve the targeted level of sedation.
For patients over 65 years of age: a dose reduction should be considered [see Use in Specific Populations].
For adult patients with impaired hepatic function: a dose reduction should be considered [see Use in Specific Populations, Clinical Pharmacology].
Due to possible pharmacodynamic interactions, a reduction in dosage of Dexmedetomidine Hydrochloride Injection or other concomitant anesthetics, sedatives, hypnotics or opioids may be required when co-administered [see Drug Interactions].
Dosage reductions may need to be considered for adult patients with hepatic impairment and geriatric patients [see Warnings and Precautions , Use in Specific Populations , Clinical Pharmacology].
Preparation of Solution
Strict aseptic technique must always be maintained during handling of Dexmedetomidine Hydrochloride Injection.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Dexmedetomidine Hydrochloride Injection, 200 mcg/2 mL (100 mcg/mL) must be diluted with 0.9% sodium chloride injection to achieve required concentration (4 mcg/mL) prior to administration. Preparation of solutions is the same, whether for the loading dose or maintenance infusion.
To prepare the infusion, withdraw 2 mL of Dexmedetomidine Hydrochloride Injection, and add to 48 mL of 0.9% sodium chloride injection to a total of 50 mL. Shake gently to mix well.
Administration with Other Fluids
Dexmedetomidine Hydrochloride Injection infusion should not be co-administered through the same intravenous catheter with blood or plasma because physical compatibility has not been established.
Dexmedetomidine Hydrochloride Injection has been shown to be incompatible when administered with the following drugs: amphotericin B, diazepam.
Dexmedetomidine Hydrochloride Injection has been shown to be compatible when administered with the following intravenous fluids:
- 0.9% sodium chloride in water
- 5% dextrose in water
- 20% mannitol
- Lactated Ringer’s solution
- 100 mg/mL magnesium sulfate solution
- 0.3% potassium chloride solution
Compatibility with Natural Rubber
Compatibility studies have demonstrated the potential for absorption of Dexmedetomidine Hydrochloride Injection to some types of natural rubber. Although Dexmedetomidine Hydrochloride Injection is dosed to effect, it is advisable to use administration components made with synthetic or coated natural rubber gaskets.
Dosage Forms and Strengths
Dexmedetomidine Hydrochloride Injection, 200 mcg (dexmedetomidine)/2 mL [100 mcg (dexmedetomidine)/mL] in a glass vial. To be used after dilution.
Warnings and Precautions
Dexmedetomidine Hydrochloride Injection 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 Injection, patients should be continuously monitored while receiving Dexmedetomidine Hydrochloride Injection.
Hypotension, Bradycardia, and Sinus Arrest
Clinically significant episodes of bradycardia and sinus arrest have been reported with Dexmedetomidine Hydrochloride Injection 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 Dexmedetomidine Hydrochloride Injection infusion. If medical intervention is required, treatment may include decreasing or stopping the infusion of Dexmedetomidine Hydrochloride Injection, increasing the rate of intravenous fluid administration, elevation of the lower extremities, and use of pressor agents. Because Dexmedetomidine Hydrochloride Injection 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 Dexmedetomidine Hydrochloride Injection-induced bradycardia. However, in some patients with significant cardiovascular dysfunction, more advanced resuscitative measures were required.
Caution should be exercised when administering Dexmedetomidine Hydrochloride Injection to patients with advanced heart block and/or severe ventricular dysfunction. Because Dexmedetomidine Hydrochloride Injection 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 Dexmedetomidine Hydrochloride Injection an additive pharmacodynamic effect was not observed. Nonetheless, caution should be used when such agents are administered concomitantly with Dexmedetomidine Hydrochloride Injection.
Transient hypertension has been observed primarily during the loading dose in association with the initial peripheral vasoconstrictive effects of Dexmedetomidine Hydrochloride Injection. Treatment of the transient hypertension has generally not been necessary, although reduction of the loading infusion rate may be desirable.
Some patients receiving Dexmedetomidine Hydrochloride Injection 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.
In adult subjects, withdrawal symptoms were not seen after discontinuation of short-term infusions of Dexmedetomidine Hydrochloride Injection (< 6 hours).
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].
Since Dexmedetomidine Hydrochloride Injection clearance decreases with severity of hepatic impairment, dose reduction should be considered in patients with impaired hepatic function [see Dosageand Administration].
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 Dexmedetomidine Hydrochloride Injection 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 procedural sedation studies include hypotension, bradycardia and dry mouth.
Adverse reaction information is derived from the two trials for procedural sedation [see Clinical Studies] in which 318 adult patients received Dexmedetomidine Hydrochloride Injection. 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 2. 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 Dexmedetomidine Hydrochloride Injection and comparator groups in both studies.
Injection (N = 318) (%)
|Placebo (N = 113) (%)|
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.
The following adverse reactions have been identified during post approval use of Dexmedetomidine Hydrochloride Injection. 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 Injection during post approval use of the drug.
|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|
|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|
Anesthetics, Sedatives, Hypnotics, Opioids
Co- administration of Dexmedetomidine Hydrochloride Injection 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 Dexmedetomidine Hydrochloride Injection and isoflurane, propofol, alfentanil and midazolam have been demonstrated. However, due to possible pharmacodynamic interactions, when co-administered with Dexmedetomidine Hydrochloride Injection, a reduction in dosage of Dexmedetomidine Hydrochloride Injection or the concomitant anesthetic, sedative, hypnotic or opioid may be required.
In one study of 10 healthy adult volunteers, administration of Dexmedetomidine Hydrochloride Injection 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.
Use in Specific Populations
Pregnancy Category C
There are no adequate and well-controlled studies of Dexmedetomidine Hydrochloride Injection 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 Injection 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.
Labor and Delivery
The safety of Dexmedetomidine Hydrochloride Injection during labor and delivery has not been studied.
It is not known whether Dexmedetomidine Hydrochloride Injection is excreted in human milk. Radio - labeled dexmedetomidine administered subcutaneously to lactating female rats was excreted in milk. Because many drugs are excreted in human milk, caution should be exercised when Dexmedetomidine Hydrochloride Injection is administered to a nursing woman.
Safety and efficacy have not been established for Procedural Sedation in pediatric patients. Additional information describing clinical studies in a different indication in which efficacy was not demonstrated in pediatric patients is approved for Hospira’s dexmedetomidine injection. However, due to Hospira’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. The use of dexmedetomidine for procedural sedation in pediatric patients has not been evaluated.
A total of 131 patients in the clinical studies were 65 years of age and over. A total of 47 patients were 75 years of age and over. Hypotension occurred in a higher incidence in Dexmedetomidine Hydrochloride Injection-treated patients 65 years or older (72%) and 75 years or older (74%) as compared to patients < 65 years (47%). A reduced loading dose of 0.5 mcg/kg given over 10 minutes is recommended and a reduction in the maintenance infusion should be considered for patients greater than 65 years of age.
Since Dexmedetomidine Hydrochloride Injection clearance decreases with increasing severity of hepatic impairment, dose reduction should be considered in patients with impaired hepatic function [see Dosage and Administration and Clinical Pharmacology].
Drug Abuse and Dependence
Dexmedetomidine hydrochloride is not a controlled substance.
The dependence potential of Dexmedetomidine Hydrochloride Injection has not been studied in humans. However, since studies in rodents and primates have demonstrated that Dexmedetomidine Hydrochloride Injection exhibits pharmacologic actions similar to those of clonidine, it is possible that Dexmedetomidine Hydrochloride Injection may produce a clonidine-like withdrawal syndrome upon abrupt discontinuation [see Warnings and Precautions (5.5)].
The tolerability of Dexmedetomidine Hydrochloride Injection was studied in one study in which healthy adult subjects were administered doses at and above the recommended dose of 0.2 to 0.7 mcg/kg/hr. The maximum blood concentration achieved in this study was approximately 13 times the upper boundary of the therapeutic range. The most notable effects observed in two subjects who achieved the highest doses were first degree atrioventricular block and second degree heart block. No hemodynamic compromise was noted with the atrioventricular block and the heart block resolved spontaneously within one minute.
One patient who received a loading bolus dose of undiluted Dexmedetomidine Hydrochloride Injection (19.4 mcg/kg), had cardiac arrest from which he was successfully resuscitated.
How Supplied/Storage and Handling
Dexmedetomidine Hydrochloride Injection, is a clear, colorless solution available as:
|Product No.||NDC No.||Strength|
|PRX462102||63323-421-16||200 mcg (dexmedetomidine) per 2 mL(100 mcg (dexmedetomidine) per mL)||2 mL single dose vial, packaged in trays of 25.|
Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
The container closure is not made with natural rubber latex.
Discard unused portion.
Patient Counseling Information
Dexmedetomidine Hydrochloride Injection is indicated for short-term intravenous sedation. Dosage must be individualized and titrated to the desired clinical effect. Blood pressure, heart rate and oxygen levels will be monitored both continuously during the infusion of Dexmedetomidine Hydrochloride Injection and as clinically appropriate after discontinuation.
When Dexmedetomidine Hydrochloride Injection is infused for more than 6 hours, patients should be informed to report nervousness, agitation, and headaches that may occur for up to 48 hours.
Additionally, patients should be informed to report symptoms that may occur within 48 hours after the administration of Dexmedetomidine Hydrochloride Injection such as: weakness, confusion, excessive sweating, weight loss, abdominal pain, salt cravings, diarrhea, constipation, dizziness or light-headedness.
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