Dexmedetomidine

Name: Dexmedetomidine

Warnings

Contraindications

Hypersensitivity

Cautions

Continuously monitor patients while on therapy; therapy should be administered only by persons skilled in the management of patients in the intensive care or operating room setting

Bradycardia and sinus arrest have occurred in young healthy volunteers with high vagal tone or with different routes of administration, including rapid intravenous or bolus administration

Transient hypertension reported primarily during loading dose; consider reduction in loading infusion rate

Patients can become aroused/alert with stimulation; this alone should not be considered as lack of efficacy

Prolonged exposure to dexmedetomidine beyond 24 hours may be associated with tolerance and tachyphylaxis and a dose-related increase in adverse events (eg, ARDS, respiratory failure, agitation)

Use with caution in hepatic impairment; consider dose reduction

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

Use with caution with concomitant administration of other vasodilators or negative chronotropic agents; use with caution due to additive pharmacodynamic effects

Withdrawal symptoms after discontinuation reported when administered for longer than 6 hr; most common events reported include nausea, vomiting, and agitation

In adult subjects, tachycardia and hypertension reported, requiring intervention 48 hr following study drug discontinuation; if tachycardia and/or hypertension occurs after discontinuation, supportive therapy is indicated

What happens if I miss a dose?

Because you will receive dexmedetomidine in a clinical setting, you are not likely to miss a dose.

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Generic: 400 mcg/4 mL (4 mL); 1000 mcg/10 mL (10 mL)

Solution, Intravenous [preservative free]:

Precedex: 400 mcg/100 mL (100 mL); 200 mcg/2 mL (2 mL) [additive free, latex free]

Precedex: 200 mcg/50 mL (50 mL) [latex free]

Precedex: 80 mcg/20 mL (20 mL)

Generic: 200 mcg/2 mL (2 mL)

Onset of Action

IV loading dose: 5 to 10 minutes

Intranasal: 45 to 60 minutes (Yuen 2007), may be faster in pediatric patients when administered via an atomizing device (Talon 2009)

Peak effect:

IV loading dose: 15 to 30 minutes

Intranasal: 90 to 105 minutes (Yuen 2007)

Time to Peak

Serum: Intranasal: Median: 38 minutes (range: 15 to 60 minutes) (Iirola 2011)

Contraindications

There are no contraindications listed in the U.S. manufacturer's labeling.

Canadian labeling: Hypersensitivity to dexmedetomidine or any component of the formulation.

Dosing Hepatic Impairment

There are no specific dosage adjustments provided in the manufacturer’s labeling; however, consider a dose reduction. Clearance is reduced in varying degrees based on the level of impairment.

Administration

Administer using a controlled infusion device. Advisable to use administration components made with synthetic or coated natural rubber gaskets. If loading dose used, administer over 10 minutes; may extend to 20 minutes to further reduce vasoconstrictive effects. Titration no more frequently than every 30 minutes may reduce the incidence of hypotension when used for ICU sedation (Gerlach 2009).

Warnings/Precautions

Concerns related to adverse effects:

• Cardiovascular effects: Episodes of bradycardia, hypotension, and sinus arrest have been associated with rapid IV administration (eg, bolus administration) or when given to patients with high vagal tone. When used for ICU sedation, use of a loading dose is optional; for the maintenance infusion, titration no more frequently than every 30 minutes may reduce the incidence of hypotension (Gerlach 2009). If medical intervention is required, treatment may include stopping or decreasing the infusion, increasing the rate of IV fluid administration, use of pressor agents, and elevation of the lower extremities. At low concentrations, mean arterial pressure (MAP) may be reduced without changes in other hemodynamic parameters (eg, pulmonary artery occlusion pressure [PAOP]); however, at higher concentrations (>1.9 ng/mL), MAP, CVP, PAOP, PVR, and SVR increase (Ebert 2000).

• Transient hypertension: Has been primarily observed during loading dose administration and is associated with the initial peripheral vasoconstrictive effects of dexmedetomidine. Treatment is generally unnecessary; however, reduction of infusion rate may be required.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with heart block, bradycardia, severe ventricular dysfunction, hypovolemia, or chronic hypertension. In a scientific statement from the American Heart Association, dexmedetomidine has been determined to be an agent that may exacerbate underlying myocardial dysfunction (magnitude: moderate) (AHA [Page 2016]).

• Diabetes: Use with caution in patients with diabetes mellitus; cardiovascular adverse events (eg, bradycardia, hypotension) may be more pronounced.

• Hepatic impairment: Use with caution in patients with hepatic impairment; dosage reductions recommended.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Use with caution in the elderly; cardiovascular events (eg, bradycardia, hypotension) may be more pronounced. Dose reduction may be necessary.

Other warnings/precautions:

• Arousability: Patients may be arousable and alert when stimulated. This alone should not be considered as lack of efficacy in the absence of other clinical signs/symptoms.

• Experienced personnel: Should be administered only by persons skilled in management of patients in intensive care setting or operating room. Patients should be continuously monitored.

• Tolerance and tachyphylaxis: Use of infusions >24 hours has been associated with tolerance and tachyphylaxis and dose-related increase in adverse reactions.

• Withdrawal: When withdrawn abruptly in patients who have received >24 hours of therapy, withdrawal symptoms may result (eg, hypertension, tachycardia, nervousness, nausea, vomiting, agitation, headaches). Use for >24 hours is not recommended by the manufacturer.

Pregnancy Risk Factor C Pregnancy Considerations

Adverse effects have been observed in some animal reproduction studies. Dexmedetomidine is expected to cross the placenta. Information related to use during pregnancy is limited (El-Tahan 2012).

What Is Dexmedetomidine?

Dexmedetomidine is a sedative that is used to sedate a patient who is under intensive medical care and needs a mechanical ventilator (breathing machine).

Before a ventilator is used, a breathing tube must be inserted through the mouth and into the patient's airway, a procedure called intubation. The tube is then attached to the ventilator, which pumps air slowly into the lungs to control the patient's breathing. Sedation with dexmedetomidine can help keep the patient relaxed and comfortable while the ventilator and tube are in place.

Dexmedetomidine is also used during anesthesia to get a patient ready for a surgery or other medical procedure.

Dexmedetomidine may also be used for purposes not listed in this medication guide.

Before dexmedetomidine is given, the doctor should know about all the patient's medical conditions or allergies, and all other medicines the patient is using. Also make sure the doctor knows if the patient is pregnant or breast-feeding.

You should not be treated with dexmedetomidine if you are allergic to it.

To make sure dexmedetomidine is safe to give, tell the doctor if the patient has:

  • liver disease;
  • diabetes;
  • high blood pressure;
  • a serious heart condition such as severe heart block, or "AV block";
  • a heart rhythm disorder; or
  • low blood pressure, or if the patient may be dehydrated.

It is not known whether this medicine will harm an unborn baby. Tell the doctor if the patient is pregnant or plan to become pregnant.

The patient should not breast-feed within 10 hours after receiving dexmedetomidine. If a breast pump is used during this time, any milk collected should be thrown out and not fed to a baby.

Dexmedetomidine Breastfeeding Warnings

A decision should be made to discontinue breastfeeding or to discontinue the drug, taking into account the importance of the drug to the mother. Excreted into human milk: Unknown Excreted into animal milk: Yes Comments: Drug administered subcutaneously to lactating female animals was distributed to, but did not accumulate in milk.

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