Dexmeto

Clear solution, colorless, free from visible impurities.
Each mL contains: Dexmedetomidine HCl equivalent to Dexmedetomidine 100 mcg.
Excipients/Inactive Ingredients: Sodium Chloride, WFI.

Pharmacology: Dexmedetomidine is a relatively selective alpha-adrenoceptor agonist with sedative properties. Respiratory rate and oxygen saturation remained within normal limits and there was no evidence of respiratory depression when Dexmedetomidine was administered by IV infusion at doses within the recommended dose range (0.2 - 0.7 mcg/kg/hr).
Gender: There was no observed difference in dexmedetomidine pharmacokinetics due to gender.
Geriatrics: The pharmacokinetic profile of dexmedetomidine was not altered by age. There were no differences in the pharmacokinetics of dexmedetomidine in young (18-40 years), middle aged (41-65 years) and elderly (>65 years) subjects.
Renal Impairment: Since the majority of metabolites are excreted in the urine, it is possible that the metabolites may accumulate upon long-term infusions in patients with impaired renal function (see Precautions, Dosage & Administration).
Hepatic Impairment: In subjects with varying degrees of hepatic impairment (Child-Pugh Class A, B, or C), clearance values for dexmedetomidine were lower than in healthy subjects.
Although dexmedetomidine is dosed to effect, it may be necessary to consider dose reduction in patients with hepatic impairment (see Hepatic Impairment under Precautions and Dosage & Administration).

Dexmedetomidine is indicated for sedation of initially intubated and mechanically ventilated patients during treatment in an intensive care setting. Dexmedetomidine should be administered by continuous infusion not to exceed 24 hours.

Dexmedetomidine should be administered using a controlled infusion device.
Dexmedetomidine dosing should be individualized and titrated to the desired clinical effect. For adult patients, dexmedetomidine is generally initiated with a loading infusion of 1 mcg/kg over 10 minutes, followed by a maintenance infusion of 0.2 to 0.7 mcg/kg/hr. The rate of the maintenance infusion should be adjusted to achieve the desired level of sedation.
Dexmedetomidine is not indicated for infusions lasting longer than 24 hours.
Dexmedetomidine has been continously infused in mechanically ventilated patients prior to extubation, during extubation, and post-extubation. It is not necessary to discontinue dexmedetomidine prior to extubation provided the infusion does not exceed 24 hours.
Dosage Adjustment: Dosage reductions may need to be considered for patients with renal impairment and hepatic impairment (see Pharmacology under Actions and Hepatic Impairment under Precautions).
Dilution Prior to Administration: Dexmedetomidine must be diluted in 0.9% sodium chloride solution 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 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: Compatibility of dexmedetomidine with co-administration of blood, serum, or plasma has not been established. Dexmedetomidine has been shown to be compatible when administered with the following intravenous fluids and drugs: 5% dextrose in water, 0.9% sodium chloride in water, alfentanil hydrochloride, amikacin sulfate, aminophylline, amiodarone hydrochloride, ampicillin sodium, sulbactam sodium, atracurium besylate, atropine sulfate, azithromycin, aztreonam, bretylium tosylate, bumetanide, butorphanol tartrate, calcium gluconate, cefazolin sodium, cefepime hydrochloride, cefoperazone sodium, cefotaxime sodium, cefotetan sodium, cefoxitin sodium, ceftazidime, ceftizoxime sodium, ceftriaxone sodium, cefuroxime sodium, chlorpromazine hydrochloride, cimetidine hydrochloride, ciprofloxacin, cisatracurium besylate, clindamycin phosphate, dexamethasone sodium phosphate, digoxin, diltiazem hydrochloride, diphenhydramine hydrochloride, dobutamine hydrochloride, dolasetron mesylate, dopamine hydrochloride, doxycycline hyclate, droperidol, enalaprilat, ephedrine hydrochloride, epinephrine hydrochloride, erythromycin lactobionate, esmolol, etomidate, famotidine, fenoldopam mesylate, fentanyl citrate, fluconazole, furosemide, gatifloxacin, gentamicin sulfate, glycopyrrolate bromide, granisetron hydrochloride, haloperidol lactate, heparin sodium, hydrocortisone sodium succinate, hydromorphone hydrochloride, hydroxyzine hydrochloride, inamrinone lactate, isoproterenol hydrochloride, ketorolac tromethamine, labetalol, lactated Ringer's solution, levofloxacin, lidocaine hydrochloride, linezolid, lorazepam, magnesium sulfate, meperidine hydrochloride, methylprednisolone sodium succinate, metoclopramide hydrochloride, metronidazole, midazolam, milrinone lactate, mivacurium chloride, morphine sulfate, nalbuphine hydrochloride, nitroglycerin, norepinephrine bitartrate, ofloxacin, ondansetron hydrochloride, pancuronium bromide, phenylephrine HCl, piperacillin sodium, piperacillin sodium-tazobactam sodium, potassium chloride, procainamide hydrochloride, prochlorperazine edisylate, promethazine hydrochloride, propofol, ranitidine hydrochloride, rapacuronium bromide, remifentanil hydrochloride, rocuronium bromide, sodium bicarbonate, sodium nitroprusside, succinylcholine, sufentanil citrate, sulfamethoxazole-trimethoprim, theophylline, thiopental sodium, ticarcillin disodium, ticarcillin disodium-clavulanate potassium, tobramycin sulfate, vancomycin hydrochloride, vecuronium bromide, verapamil hydrochloride, and a plasma-substitute.
Dexmedetomidine has been shown to be incompatible when administered with the following drugs: amphotericin B, diazepam.

No hemodynamic compromises was noted with the AV block and the heart block resolved spontaneously within one minute.

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

Reports of hypotension and bradycardia have been associated with dexmedetomidine infusion. If medical intervention is required, treatment may include decreasing or stopping the infusion of dexmedetomidine, increasing the rate of IV fluid administration, elevation of the lower extremities, and use of pressor agents. Because dexmedetomidine has the potential to augment bradycardia induced by vagal stimuli, clinicians should be prepared to intervene. The intravenous administration of anticholinergic agents (e.g., atropine) should be considered to modify vagal tone. Atropine or glycopyrrolate were effective in the treatment of most episodes of dexmedetomidine induced bradycardia. However, in some patients with significant cardiovascular dysfunction, more advanced resuscitative measures were required.
Caution should be exercised when administering dexmedetomidine to patients with advanced heart block and/or severe ventricular dysfunction. Because dexmedetomidine decreases sympathetic nervous system activity, hypotension and/or bradycardia may be expected to be more pronounced in hypovolemic patients and in those with diabetes mellitus or chronic hypertension and in the elderly.
In situations where other vasodilators or negative chronotropic agents are administered, co-administration of dexmedetomidine could have an additive pharmacodynamic effect and should be administered with caution.
Treatment of the transient hypertension has generally not been necessary, although reduction of the loading infusion rate may be desirable.
Dexmedetomidine infusion should not be co-administered through the same IV catheter with blood or plasma because physical compatibility has not been evaluated in infusions over 24 hours.
Dexmedetomidine is not indicated for infusions lasting over 24 hours (see Indications, Dosage & Administration).
Withdrawal: If dexmedetomidine is administered chronically and stopped abruptly, withdrawal symptoms similar to those reported for another alpha-2-adrenergic agent, clonidine, may result. These symptoms include nervousness, agitation, and headaches, accompanied or followed by a rapid rise in blood pressure and elevated catecholamine concentrations in the plasma.
Dexmedetomidine should not be administered for greater than 24 hours (see Indications, Dosage & Administration).
Drug Abuse and Dependence: Dexmedetomidine (dexmedetomidine hydrochloride) is not a controlled substance.
The dependence potential of dexmedetomidine has not been studied in humans. However, dexmedetomidine exhibits pharmacologic actions similar to those of clonidine, it is possible that dexmedetomidine may produce a clonidine-like withdrawal syndrome upon abrupt discontinuation (see withdrawal as previously mentioned).
Hepatic Impairment: Since dexmedetomidine clearance decreases with severity of hepatic impairment, dose reduction should be considered in patients with impaired hepatic function (see Pharmacology under Actions, Dosage & Administration).
Use in Children: There have been no clinical studies to establish the safety and efficacy of dexmedetomidine in pediatric patients below 18 years of age. Therefore, dexmedetomidine is not recommended for use in this population.
Use in the Elderly: A dose reduction may be considered in patients over 65 years of age.
Dexmedetomidine is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection in elderly patients, and it may be useful to monitor renal function.

Pregnancy: Teratogenic Effects: Pregnancy Category C: There are no adequate and well-controlled studies in pregnant women. Dexmedetomidine should be used during pregnancy only if the potential benefits justify the potential risk to the fetus.
Labor and delivery: The safety of dexmedetomidine during labor and delivery has not been studied. Therefore, dexmedetomidine is not recommended during labor and delivery including cesarean section deliveries.
Nursing mothers: It is not known whether dexmedetomidine is excreted in human milk. Because many drugs are excreted in human milk, caution should be excercised when dexmedetomidine is administered to a nursing woman.

The most frequently observed treatment-emergent adverse events included hypotension, hypertension, nausea, bradycardia, fever, vomiting, hypoxia, tachycardia and anemia.
The treatment-emergent adverse events in the table as follows were reported in ≤1% of all dexmedetomidine-treated patients that are potentially clinically relevant. (See table.)


Click on icon to see table/diagram/image

General: No evidence of cytochrome P450 mediated drug interactions that are likely to be of clinical relevance.
Anesthetics/Sedatives/Hypnotics/Opioids: Co-administration of dexmedetomidine 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 and isoflurane, propofol, alfentanil and midazolam has been demonstrated. However, due to possible pharmacodynamic interactions, when co-administered with dexmedetomidine, a reduction in dosage of dexmedetomidine or the concomitant anesthetic, sedative, hypnotic or opioid may be required.

Handling Procedures: Parenteral products should be inspected visually for particulate matter and discoloration prior to administration. Strict aseptic technique must always be maintained during handling of dexmedetomidine. Vials are intended for single use only.
Dexmedetomidine must be diluted in 0.9% sodium chloride solution to achieve the required concentrations prior to administration. Preparation of solutions is the same, whether for the loading dose or maintenance infusion (see Dosage & Administration).

Store at temperature below 25°C. Keep the vial in the original box when not in use.
The solution that has been diluted in 0.9% NaCl infusion solution is stable for 24 hours at a temperature below 30°C.

Hypnotics & Sedatives

N05CM18 - dexmedetomidine ; Belongs to the class of other hypnotics and sedatives.

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