Precedex

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  • Anesthetics
PAGE CONTENTS
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  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Precedex Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Dexmedetomidine HCl 100mcg/mL; soln for IV infusion after dilution.

    Pharmacological Class

    Alpha-2 agonist.

    See Also

    How Supplied

    Single-dose vials (100mcg/mL)—25 (2mL); Single-dose vials (4mcg/mL)—10 (each 20mL); Single-dose bottles (4mcg/mL)—20 (50mL), 10 (100mL), 1 (250mL) 

    How Supplied

    Precedex

    • Precedex (dexmedetomidine hydrochloride) injection 200 mcg/2 mL (100 mcg/mL) is clear and colorless. The strength is based on the dexmedetomidine base. 

    • Supplied as a tray of 25 single-dose clear glass vials.

    Precedex in sodium chloride

    • Precedex (dexmedetomidine hydrochloride in 0.9% Sodium Chloride) injection (4 mcg/mL) is clear and colorless. The strength is based on the dexmedetomidine base.

    • Supplied as:

      • 80 mcg/20 mL (4 mcg/mL) concentration in a carton of 10 single-dose clear glass vials.

      • 200 mcg/50 mL (4 mcg/mL) concentration in a tray of 20 single-dose clear glass bottles.

      • 400 mcg/100 mL (4 mcg/mL) concentration in a tray of 10 single-dose clear glass bottles.

      • 1000 mcg/250 mL (4 mcg/mL) concentration in a carton of 1 single-dose clear glass bottle.

    Storage

    • Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature.]

    Manufacturer

    Hospira

    Generic Availability

    YES

    Mechanism of Action

    Precedex is a relatively selective alpha2-adrenergic agonist with sedative properties. Alpha2 selectivity is observed in animals following slow intravenous infusion of low and medium doses. Both alpha1 and alpha2 activity is observed following slow intravenous infusion of high doses or with rapid intravenous administration.

    Precedex Indications

    Indications

    For sedation of initially intubated and mechanically ventilated adult patients during treatment in an intensive care setting. For sedation of non-intubated adult patients prior to and/or during surgical and other procedures. For sedation of non-intubated pediatric patients aged 1 month to <18 years prior to and during non-invasive procedures.

    Precedex Dosage and Administration

    Adult

    Individualize. Give by continuous infusion not to exceed 24hrs. Initiation of ICU sedation: loading infusion of 1mcg/kg over 10mins; patients converting from alternate sedative therapy: a loading dose may not be required; >65yrs, hepatic impairment: reduce dose. Maintenance of ICU sedation: 0.2–0.7mcg/kg/hr; >65yrs, hepatic impairment: reduce dose. Initiation of procedural sedation: loading infusion of 1mcg/kg over 10mins, less invasive procedures: 0.5mcg/kg over 10mins; awake fiberoptic intubation patients: loading infusion of 1mcg/kg over 10mins; >65yrs: loading infusion of 0.5mcg/kg over 10mins; hepatic impairment: reduce dose. Maintenance of procedural sedation: initially 0.6mcg/kg/hr and titrated to achieve desired effect with doses ranging from 0.2–1mcg/kg/hr; awake fiberoptic intubation patients: 0.7mcg/kg/hr until endotracheal tube is secured; >65yrs, hepatic impairment: reduce dose.

    Children

    Initiation of ICU or other surgical procedural sedation: not established. Initiation of sedation during non-invasive procedures: <1month: not established. Individualize. Give by continuous infusion not to exceed 24hrs. 1month–<2yrs: loading infusion of 1.5mcg/kg over 10mins; 2yrs–<18yrs: loading infusion of 2mcg/kg over 10mins; consider dose reduction if clinically indicated. Maintenance of sedation during non-invasive procedures (1month–<18yrs): initially 1.5mcg/kg/hr and titrated to achieve desired effect with doses ranging from 0.5–1.5mcg/kg/hr; titrate as clinically warranted based on response.

    Precedex Contraindications

    Not Applicable

    Precedex Boxed Warnings

    Not Applicable

    Precedex Warnings/Precautions

    Warnings/Precautions

    Should be administered by persons skilled in management of patients in intensive care or operating room setting. Advanced heart block and/or severe ventricular dysfunction. Hypovolemia, diabetes, chronic hypertension, elderly: increased risk of bradycardia and hypotension. Withdrawal symptoms (adults: within 24-48hrs after infusion discontinued; children: after infusions <2hrs). Discontinue if hyperthermia or pyrexia is suspected; monitor. Hepatic impairment. Pregnancy. Nursing mothers: monitor infants.

    Pregnancy Considerations

    Risk Summary

    • Available data from trials and case reports have not identified a drug-associated risk for major birth defects and miscarriage. However, the reported exposures occurred after the first trimester.

    Nursing Mother Considerations

    Risk Summary

    • Available published literature reports the presence of dexmedetomidine in human milk after IV administration. No information regarding the effects of dexmedetomidine on the breastfed infant or the effects on milk production. 

    • Monitor the breastfed infant for irritability. Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for Precedex and any potential adverse effects on the breastfed infant from Precedex or from the underlying condition.

    Pediatric Considerations

    Sedation for Non-Invasive Procedures 

    • Safety and effectiveness have not been established in pediatric patients less than 1 month of age.

    ICU Sedation

    • Safety and efficacy have not been established in pediatric patients.

    Geriatric Considerations

    Intensive Care Unit Sedation  

    • Consider dose reduction in patients over 65 years of age.

    Procedural Sedation 

    • For patients over 65 years of age: reduce loading dose to 0.5 mcg/kg over 10 minutes and consider a reduction in the maintenance infusion.

    Hepatic Impairment Considerations

    • Consider a dose reduction since Precedex clearance decreases with increasing severity of hepatic impairment.

    Precedex Pharmacokinetics

    Distribution

    • Steady-state volume of distribution: approximately 118 L.

    • 94% average protein binding.

    Metabolism

    • Hepatic.

    • Major metabolic pathways are: direct N-glucuronidation; aliphatic hydroxylation (mediated primarily by CYP2A6 with a minor role of CYP1A2, CYP2E1, CYP2D6, and CYP2C19); and N-methylation.

    Elimination

    • Renal (95%), fecal (4%).

    • Clearance: approximately 39 L/h.

    • Half-life: approximately 2 hours.

    Precedex Interactions

    Interactions

    Additive effects with other vasodilators, negative chronotropic agents, anesthetics, sedatives, hypnotics, opioids; consider reducing dose. Incompatible with amphotericin B or diazepam; avoid co-administration.

    Precedex Adverse Reactions

    Adverse Reactions

    Hypotension, bradycardia, dry mouth, bradypnea, hypertension; sinus arrest, transient hypertension (w. loading dose).

    Precedex Clinical Trials

    Clinical Trials

    Intensive Care Unit Sedation 

    Adult Patients

    2 randomized, double-blind, parallel-group, placebo-controlled multicenter clinical trials (Study 1 and 2) included 754 adult patients being treated in a surgical intensive care unit. All patients were initially intubated and received mechanical ventilation. These trials evaluated the sedative properties of Precedex by comparing the amount of rescue medication (midazolam in one trial and propofol in the second) required to achieve a specified level of sedation (using the standardized Ramsay Sedation Scale) between Precedex and placebo from onset of treatment to extubation or to a total treatment duration of 24 hours. 

    Study 1

    • Adult patients were randomly assigned to receive placebo (n=175) or Precedex (n=178) by intravenous (IV) infusion at a dose of 0.4 mcg/kg/hr (with allowed adjustment between 0.2 and 0.7 mcg/kg/hr after an initial loading dose of 1 mcg/kg IV over 10 minutes. The study drug infusion rate was adjusted to maintain a Ramsay sedation score of ≥3. Patients were allowed to receive “rescue” midazolam as needed to augment the study drug infusion. Midazolam was used significantly more among patients in the placebo arm compared with those in the Precedex arm.

    • In a second prospective primary analysis, the sedative effects of Precedex were compared with the percentage of adult patients who achieved a Ramsay sedation score of ≥3 during intubation without the use of additional rescue medication. A significantly greater percentage of adult patients in the Precedex arm maintained a Ramsay sedation score of ≥3 without receiving any midazolam rescue compared to the placebo arm.

    • In a prospective secondary analysis, a dose of morphine sulfate was assessed among adults in the Precedex and placebo arms. Patients in the Precedex arm received less morphine sulfate for pain  compared with those in the placebo arm. Moreover, there was a greater proportion of Precedex-treated patients who received no morphine sulfate for pain compared with placebo-treated patients (44% vs 19%, respectively).

    Study 2

    • Adult patients were randomly assigned to receive placebo (n=198) or Precedex (n=203) by IV infusion at a dose of 0.4 mcg/kg/hr (with allowed adjustment between 0.2 and 0.7 mcg/kg/hr after an initial loading dose of 1 mcg/kg IV over 10 minutes. The study drug infusion rate was adjusted to maintain a Ramsay sedation score of ≥3. Patients were allowed to receive “rescue” propofol as needed to augment the study drug infusion. 

      • Propofol was used significantly more among patients in the placebo arm compared with those in the Precedex arm. 

      • A significantly greater percentage of adult patients in the Precedex group compared to the placebo group maintained a Ramsay sedation score of ≥3 without receiving any propofol rescue.

    • In a prospective secondary analysis, a dose of morphine sulfate was assessed among adults in the Precedex and placebo arms. Patients in the Precedex arm received less morphine sulfate for pain  compared with those in the placebo arm. Moreover, there was a greater proportion of Precedex-treated patients who received no morphine sulfate for pain compared with placebo-treated patients (41% vs 15%, respectively).

    A controlled clinical trial also compared Precedex to midazolam in ICU sedation exceeding 24 hours duration. Precedex did not achieve superiority to midazolam for the primary efficacy endpoint of the percentage of time patients were adequately sedated (81% vs 81%).

     

    Procedural Sedation

    Adult Patients

    2 randomized, double-blind, placebo-controlled multicenter clinical trials (Study 1 and 2) evaluated the efficacy and safety of Precedex for sedation of non-intubated adults prior to and/or during surgical and other procedures.

    Study 1

    • Study 1 evaluated the sedative properties of Precedex in adults having a variety of elective surgeries/procedures performed under monitored anesthesia care.

    • The sedative properties of Precedex were evaluated by comparing the percent of adult patients not requiring rescue midazolam to achieve a specified level of sedation using the standardized Observer’s Assessment of Alertness/Sedation Scale. Patients were randomly assigned to receive a loading infusion of either Precedex 1 mcg/kg, Precedex 0.5 mcg/kg, or placebo (normal saline) given over 10 minutes and followed by a maintenance infusion started at 0.6 mcg/kg/hr. 

    • Precedex was more effective than the comparator arm when used to sedate non-intubated patients requiring monitored anesthesia care during surgical and other procedures.

    Study 2

    • Study 2 evaluated Precedex in adults undergoing awake fiberoptic intubation prior to a surgical or diagnostic procedure. The sedative properties of Precedex were evaluated by comparing the percent of adult patients requiring rescue midazolam to achieve or maintain a specified level of sedation using the Ramsay Sedation Scale score ≥2. 

    • Patients were randomly assigned to receive a loading infusion of Precedex 1 mcg/kg or placebo (normal saline) given over 10 minutes and followed by a fixed maintenance infusion of 0.7 mcg/kg/hr. After achieving the desired level of sedation, topicalization of the airway occurred. Adult patients were allowed to receive rescue midazolam as needed to achieve and/or maintain a Ramsay Sedation Scale ≥2.  

    •  A significantly greater percentage of adult patients in the Precedex arm maintained a Ramsay sedation score of ≥2 without receiving any midazolam rescue compared to the placebo arm (53% vs 14%).

     

    Pediatric Patients  

    • A randomized, double-blind, dose-ranging, dose-controlled multicenter clinical trial evaluated the efficacy and safety of Precedex for sedation of 122 non-intubated pediatric patients aged 1 month to less than 17 years undergoing MRI scans.

    • Patients were randomly assigned to receive Precedex low dose, middle dose, or high dose. All patients received a loading dose infusion of Precedex over 10 minutes followed by a maintenance infusion for the duration of the MRI scan. Patients were allowed to receive concomitant propofol if needed based on clinical judgement to achieve and/or maintain adequate sedation.

    • In the combined age group, 14.3% (6/42) of pediatric patients in the low dose group did not require concomitant propofol vs 63.2% (24/38) in the high dose group. The percentage of patients at the Precedex high dose who completed the MRI without concomitant propofol was statistically greater than the percentage in the Precedex low dose group (P <.001). 

    • In the Precedex high dose group, pediatric patients in both the combined and individual age group were at the target sedation rating scale score (PSSS of 2) for a mean >87% of the time during the Precedex maintenance infusion. In both the combined and individual age group, an increase in the percentage of time at the target sedation rating scale score (PSSS of 2) was observed with increasing Precedex dosage. 

    Precedex Note

    Not Applicable

    Precedex Patient Counseling

    See Literature

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