Dosing Guidelines
`for Precedex®
`
`Nonintubated Procedural Sedation
`
`and
`
`ICU Sedation
`
`0\1 Precedex®
`'=1 (dexmedetomidile HCIInjection)
`
`Petition for Inter Partes Review of US 8,455,527
`Amneal Pharmaceuticals LLC- Exhibit 1063- Page 1
`
`

`
`3
`
`loading infusion rate may be desirable.1
`generally not been necessary, although reduction of the
`vasoconstrictive effects of Precedex. Treatment has
`the loading dose in association with the initial peripheral
`• Transient hypertension has been observed primarily during
`
`pharmacodynamic effects.1
`vasodilators or negative chronotropic agents due to additive
`• Use with caution when coadministering with other
`
`ventricular dysfunction.1
`to patients with advanced heart block and/or severe
`• Caution should be exercised when administering Precedex
`
`2
`
`\:J (dexmeOO!omidile HCil'Jjectioo)
`(/'\) Precedex®
`
`Please see enclosed full Prescribing Information.
`
`glycopyrrolate or ephedrine) to modify vagal tone.1
`to intervene with anticholinergic agents (e.g., atropine,
`induced by vagal stimuli, clinicians should be prepared
`• Because Precedex has the potential to augment bradycardia
`
`•3
`
`
`
`as well as in the elderly. 1
`patients with diabetes mellitus or chronic hypertension,
`to be more pronounced in hypovolemic patients and in
`activity, hypotension and/or bradycardia may be expected
`• Because Precedex decreases sympathetic nervous system
`
`atropine or ephedrine
`
`-Use of pressor agents, such as glycopyrrolate,
`-Elevation of lower extremities
`-Increasing the rate of IV fluid administration
`-Decreasing or stopping the infusion of Precedex
`hypotension or bradycardia, treatment may include1•3:
`
`• If medical intervention is required for Precedex-induced
`
`be anticipated with Precedex.2
`• Moderate heart rate and blood pressure reductions should
`
`infusion or bolus administration.1
`different routes of administration, such as rapid intravenous
`in young, healthy volunteers with high vagal tone or with
`arrest have been associated with Precedex administration
`• Clinically significant episodes of bradycardia and sinus
`
`Cardiovascular Effects
`What to Expect
`
`dose reductions should be considered in these patient types.1
`clearance in patients with impaired hepatic or renal function,
`hypotension in the elderly, and the potential for reduced
`
`• Due to the increased incidence of bradycardia and
`dry mouth.1
`(incidence >2%) are hypotension, bradycardia and
`
`• The most common adverse reactions with Precedex
`patients should be continuously monitored.1
`
`• Due to the known pharmacologic effects of Precedex,
`
`operating room setting.1
`in the management of patients in the intensive care or
`
`• Precedex should be administered only by persons skilled
`
`not to exceed 24 hours.
`
`• Precedex should be administered by continuous infusion
`
`and other procedures.1
`nonintubated patients prior to and/or during surgical
`in an intensive care setting and for sedation of
`and mechanically ventilated patients during treatment
`• Precedex is indicated for sedation of initially intubated
`
`Precede~ Overview
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`Please see enclosed full Prescribing Information.
`
`4
`
`Patients may have received multiple forms of intervention.
`*Other possible interventions induded elevation of lower extremities.
`
`or >30% decrease from prestudy drug infusion values.
`tBradycardia was defined in pivotal trial protocols as <40 beats per minute
`
`infusion values.
`as SBP <80 mm Hg, DBP <50 mm Hg or >30% decrease from prestudy drug
`•Hypotension was defined in pivotal trial protocols in absolute and relative tenms
`
`1 ( 20fo)
`
`1 (2%)
`7 (16%)
`1 (2%)
`(n=45)
`
`12 (270fo)
`33 (73%)
`(n=45)
`
`45 (14%)
`
`1 (<1%)
`9 (5%)
`16 (9%)
`1 (<1%)
`2 (1%)
`
`55 (32%)
`(n=173)
`
`60 (35%)
`113 (65%)
`(n=173)
`
`173 (54%)
`
`Precedex Discontinued
`Precedex Dose Reduced
`IV Fluid Administration
`Dopamine
`Calcium Chloride
`Atropine
`
`ycopyrrolate
`
`Gl
`
`Ephedrine or Phenylephrine
`
`When Required*
`Type of Intervention
`
`Intervention Required
`No Intervention Required
`
`Intervention
`
`Overall Incidence
`
`in Patients Undergoing Procedural Sedation3
`Incidence and Interventions for Hypotension, Bradycardia
`
`manage these adverse events.
`at which certain types of interventions may be needed to
`experience hypotension or bradycardia and the frequency
`Precedex-sedated patients undergoing MAC sedation may
`
`• The table on page 5 shows the frequency at which
`
`intubation.1
`procedures as well as patients undergoing awake fiberoptic
`anesthesia care (MAC) sedation for a variety of surgical
`clinical trials of nonintubated patients receiving monitored
`
`• Precedex has been studied in two pivotal Phase Ill
`
`Procedural Sedation
`
`respectively. 2
`systolic and diastolic blood pressures were 10% and 11%,
`was approximately 7% and the largest mean decreases in
`with Precedex®, the largest mean decrease in heart rate
`
`•In two pivotal Phase Ill clinical trials of ICU patients treated
`
`ICU Sedation
`
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`Please see enclosed full Prescribing Information.
`
`is desired.6
`The intravenous route may be used if an immediate effect
`rapid (within 10 to 20 minutes) than by subcutaneous injection.
`Absorption (onset of action) by the intramuscular route is more
`doses should be governed by blood pressure responses.
`minimize hypotension secondary to spinal anesthesia. Repeat
`to 0.2 to 1 ml of 5% solution) is usually adequate to prevent or
`50 mg) injected subcutaneously or intramuscularly (equivalent
`intravenously. Usual adult dose: 25 to 50 mg (range 10 to
`Injection may be given subcutaneously, intramuscularly or
`Depending on the clinical circumstances, Ephedrine Sulfate
`of spinal or other types of nontopical conduction anesthesia.
`Ephedrine is indicated to counteract the hypotensive effects
`
`Bradycardia or Hypotension
`Ephedrine Dosing for Drug-induced
`
`not to exceed 10 ml of sterile water or normal saline.5
`endotracheal administration is 1 to 2 mg diluted to a total
`IV access. The recommended adult dose of atropine for
`administration of atropine can be used in patients without
`for patients with bradyasystolic cardiac arrest. Endotracheal
`The administration of this dose of atropine should be reserved
`(0.04 mg/kg) given IV is a fully vagolytic dose in most patients.
`every 3 to 5 minutes if asystole persists. Three milligrams
`dose of atropine is administered intravenously and is repeated
`demand. For patients with bradyasystolic cardiac arrest, a 1 mg
`
`6
`
`effects of atropine-induced tachycardia on myocardial oxygen
`to 3 mg (maximum 0.03 to 0.04 mg/kg) to avoid the detrimental
`coronary artery disease, the total dose should be restricted to 2
`When the recurrent use of atropine is essential in patients with
`
`in adults.5
`central or peripheral parasympathomimetic effects of low doses
`0.5 mg can produce a paradoxical bradycardia because of the
`(5-10 ml of a 0.1 mg/ml solution). Administration of less than
`Initial single doses in adults vary from around 0.5 mg to 1 mg
`
`Bradycardia or Hypotension
`Atropine Dosing for Drug-induced
`
`as needed, at intervals of 2 to 3 minutes.4
`intravenously as single doses of 0.1 mg (0.5 ml) and repeated,
`arrhythmias (e.g., bradycardia). It should be administered
`counteract drug-induced or vagal reflexes and their associated
`Glycopyrrolate Injection may be used during surgery to
`
`induced Bradycardia or Hypotension
`Glycopyrrolate Dosing for Drug(cid:173)
`
`resuscitative measures were required.1
`with significant cardiovascular dysfunction, more advanced
`of Precedex-induced bradycardia. However, in some patients
`ephedrine were effective in the treatment of most episodes
`In Precedex®clinical trials, atropine, glycopyrrolate and
`
`•3
`
`or Hypotension
`Drug-induced Bradycardia
`Treatment Options for
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`tf (dexmedetomidi'le HCitljectioo)
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`Please see enclosed full Prescribing Information.
`
`alfentanil when coadministered with Precedex.8
`impact on respiratory function can be lessened by reducing
`is needed to produce the same degree of pain relief; thus, the
`9Aifentanil. In the presence of dexmedetomidine, less alfentanil
`
`control.11
`consumption by 28% at identical pain scores compared to
`10 minutes before induction reduced postoperative morphine
`'Morphine. A single IV dose of 1 meg/kg dexmedetomidine given
`
`reduced in the presence of dexmedetomidine. 10
`required for sedation and induction of anesthesia may have to be
`of motor response by approximately one half. Propofol doses
`propofol concentrations required for sedation and suppression
`epropofol. In healthy subjects, dexmedetomidine reduced the
`
`effect of dexmedetomidine on midazolam was less pronounced.8
`sedation. At higher degrees of sedation, the augmentation of the
`with greater degrees of synergy occurring at lower levels of
`combination with dexmedetomidine on sedation was synergistic,
`dMidazolam. In healthy subjects, the effect of midazolam in
`
`as induction agents.9
`by 47% in patients who also received thiopental and alfentanil
`clsoflurane. Dexmedetomidine decreased the MAC of isoflurane
`
`50% of healthy subjects.8
`respectively, necessary to elicit the desired response in
`decreased the end-tidal isoflurane concentration by 31%-50%,
`blsoflurane. Low-and high-dose infusions of dexmedetomidine
`
`of sevoflu rane by 17% in patients undergoing elective surgery. 7
`asevoflurane. Dexmedetomidine 0.7 ng/ml decreased the MAC
`
`8
`
`observed in practice.
`compared to other trials and may not always reflect the rates
`widely varying conditions, rates observed may not be directly
`patient populations. Because clinical trials are conducted under
`These clinical trials are of different designs in a variety of
`
`sedation while taking the medications listed below.
`studies of healthy subjects and in patients undergoing
`These effects have been demonstrated in pharmacodynamic
`
`concomitant agent may be required.1
`midazolam. A decrease in the dosage of Precedex or the
`effects with sevoflurane, isoflurane, propofol, alfentanil and
`effects of these agents. Specific studies have confirmed these
`hypnotics and opioids can enhance the pharmacodynamic
`Coadministration of Precedex with anesthetics, sedatives,
`
`to Effect
`Concomitant Medications
`Titrate Precede~ and
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`tf (dexmedetomidi'le HCitljectioo)
`{]'\) Precedex~
`
`Please see enclosed full Prescribing Information.
`
`loading dose, respectively, over 10 mirutes and titrated to effect).
`'Two Precedex strengths were used in the trial (1 meg/kg loading dose and 0.5 meg/kg
`
`10
`
`as needed to maintain adequate analgesia.1
`OAA/S score ::;4.1 Patients received either morphine or fentanyl
`level of sedation, either a Ramsay Sedation Score ;?:3 or an
`Patients in each study were titrated to achieve an equivalent
`
`12
`
`•
`
`as to as·
`
`0.47
`
`0.43
`
`0.9 to 1.4*
`
`5
`
`72
`
`151
`
`0.83
`
`0.89
`
`4.1
`
`19
`
`513
`
`Fentanyl (meg)
`Study 3 MAC Sedation
`
`Morphine (mg/hr)
`Study 2 ICU Sedation
`
`Morphine (mg/hr)
`Study 1 ICU Sedation
`
`Midazolam (mg)
`Study 2 ICU Sedation
`
`Propofol (mg)
`Study 1 ICU Sedation
`
`undergoing MAC sedation.1•12
`trials of Precedex in surgicaiiCU patients and patients
`morphine in three placebo-controlled Phase Ill pivotal
`Mean total dosages of coadministered sedatives and/or
`
`control group.
`for patients receiving Precedex and patients in the placebo
`sedative and analgesics are shown in the table on page 11
`control pain. Differences in coadministered dosages of rescue
`also received concomitant morphine or fentanyl as needed to
`needed to achieve an equivalent depth of sedation. Patients
`administered the study drug as well as a rescue sedative as
`In Phase Ill placebo-controlled pivotal trials, patients were
`or the concomitant agent may be required.1
`midazolam. A decrease in the dosage of Precedex
`sevoflurane, isoflurane, propofol, alfentanil and
`Specific studies have confirmed these effects with
`the pharmacodynamic effects of these agents.
`sedatives, hypnotics and opioids can enhance
`Coadministration of Precedex® with anesthetics,
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`tf (dexmedetomidi'le HCitljectioo)
`{]'\) Precedex®
`
`Please see enclosed full Prescribing Information.
`
`was achieved after 15 to 33 minutes.13
`0.2 mcg/kg/hr, an average Ramsay Sedation Score of 3 to 4
`1 0 minutes followed by a lower maintenance infusion of
`
`• When administering a lower loading dose of 0.5 meg/kg over
`subjects.13
`20 to 25 minutes after initiating infusion in healthy normal
`an average Ramsay Sedation Score of 4 to 5 was achieved
`10 minutes followed by a maintenance infusion of 0.3 mcglkg/hr,
`
`• When a loading dose of 1 meg/kg is administered for
`
`-o-l'nlcedex 1.0 rrt::fii1tfi hr for 10 min lolowed !'¥ main1ononce irOOsion ol 0.34 ~
`-o-l'nlcedex o.s ~for 10 min lolowed ~>¥ maimonance infusion o1 0.17 ~
`
`Placebo
`
`-
`
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`40
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`35
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`30
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`25
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`20
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`15
`
`10
`
`Baseline 5
`
`Time from start of infusion (minutes)
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`2 hours.1
`The terminal elimination half-life of Precedex is approximately
`
`sedative effect may be extended.
`the infusion.13 If a loading dose is not used, time to onset of the
`of sedation generally within 10 to 15 minutes after the start of
`over a 10-minute period provides clinically effective onset
`Based on sedation scores, a loading infusion of one meg/kg
`
`with a half-life of about 6 minutes. 1
`Following infusion, Precedex exhibits a rapid distribution phase
`
`Time to Onset
`
`sedative medications.
`before determining the need for additional analgesics or
`medications to assess accurately the status of the patient
`Question the patient prior to administration of additional
`
`opioid analgesics may produce unwanted side effects. 1
`pharmacodynamic effects of sedative/hypnotic agents with
`to arouse a patient sedated with Precedex. The additive
`medications should not be based solely on the ability
`The decision to administer additional analgesics or sedative
`
`efficacy in the absence of other clinical signs and symptoms.1
`Precedex should not be considered as evidence of a lack of
`because the ability to be awakened while sedated with
`This is important for clinicians and caregivers to understand
`
`some patients were reported as arousable and alert.1
`Score ~3 or an OAA/S score ::;4. However, when stimulated,
`All patients were titrated to achieve either a Ramsay Sedation
`combination with midazolam, propofol, morphine or fentanyl.
`an equivalent level of sedation using Precedex alone or in
`In pivotal clinical trials, patients were titrated to achieve
`
`IV sedatives you are more accustomed to using.1
`sedatives, and the sedative profile may differ from that of other
`Precedex® has a different mechanism of action than other IV
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`Normal Subjects13
`Time to Sedative Onset with Precedex in Healthy
`
`Sedative Profile
`
`

`
`15
`
`tf (dexmedetomidi'le HCitljectioo)
`{]'\) Precedex~
`
`Please see enclosed full Prescribing Information.
`
`14
`
`beyond 15 minutes. 13
`dose is not used, the initiation of a sedative effect may extend
`administered over a 10 minute period. However, if a loading
`generally 10 to 15 minutes when a 1 meg/kg loading dose is
`With Precedex the time to onset of some sedative effect is
`
`of side effects. 1
`as to avoid oversedation and potential for increased incidence
`titration to determine the extent of each dosage modification so
`especially important to wait 20 to 30 minutes after each dosage
`effects of Precedex in combination with other IV sedatives it is
`Because of the potential for enhanced pharmacodynamic
`
`13
`
`•
`
`with sevoflurane, isoflurane, propofol, alfentanil and midazolam.1
`initiating Precedex. Specific studies have confirmed these effects
`Precedex or the concomitant medication may be required when
`effects of these agents and a decrease in the dosage of
`opioids with Precedex can enhance the pharmacodynamic
`Coadministration of anesthetics, sedatives, hypnotics and
`
`Transitioning from Other IV Sedatives
`of Precedex to Understand When
`Important Pharmacodynamic Properties
`
`of undersedation and an increased potential for agitation.
`therapy prior to the onset of Precedex could lead to periods
`• Decreasing/discontinuing the patient's previous IV sedative
`
`oversedation and an increased potential for side effects.1
`
`•Increasing Precedex dosages too rapidly could lead to
`full sedative effects after each dosage adjustment.13
`20 to 30 minutes) may not allow Precedex to reach its
`• Adjusting the Precedex dose too rapidly (i.e., less than
`20 to 30 minutes.13
`
`• Full sedative effect of Precedex is generally not seen for
`
`different pharmacokinetic/pharmacodynamic profiles.
`• Titrate down other concomitant sedatives as per their
`
`is 0.2 to 0.7 mcg/kg/hr.1
`0.4 meg/kg/hr. The titration range for Precedex in the ICU
`
`• Generally initiate Precedex maintenance infusion at
`
`patients are oversedated.1
`effects of Precedex are observed, or too slowly, such that
`agents are not titrated downward too quickly before the sedative
`effects. This is important to know so that preexisting sedative
`sedatives and/or opioids due to the additive pharmacodynamic
`between adding Precedex and decreasing other preexisting
`Transitioning to Precedex involves maintaining a balance
`
`Agents
`From Other IV Sedative
`Transitioning to Precedex®
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`tf (dexmedetomidi'le HCitljectioo)
`{]'\) Precedex®
`
`Please see enclosed full Prescribing Information.
`
`Also see Geriatric Use.
`
`renal function.
`accumulate upon long-term infusions in patients with impaired
`are excreted in the urine, it is possible that the metabolites may
`with impaired renal function. Since the majority of metabolites
`metabolites of Precedex have not been evaluated in patients
`to healthy subjects. However, the pharmacokinetics of the
`impairment (creatinine clearance: <30 mUmin) compared
`were not significantly different in patients with severe renal
`Precedex pharmacokinetics (Cmax, T max, AUC, t112, CL, and Vss)
`
`Renal Impairment
`with impaired hepatic function.
`impairment, dose reduction should be considered in patients
`Since Precedex clearance decreases with severity of hepatic
`
`Hepatic Impairment
`
`16
`
`useful to monitor renal function.
`be taken in dose selection in elderly patients, and it may be
`are more likely to have decreased renal function, care should
`patients with impaired renal function. Because elderly patients
`and the risk of adverse reactions to this drug may be greater in
`Precedex is known to be substantially excreted by the kidney,
`
`Geriatric Use
`Therefore, Precedex should not be used in this population.
`efficacy of Precedex in pediatric patients below 18 years of age.
`There have been no clinical studies to establish the safety and
`
`Pediatric Use
`Precedex is administered to a nursing woman.
`are excreted in human milk, caution should be exercised when
`lactating female rats was excreted in milk. Because many drugs
`Radio-labeled Precedex administered subcutaneously to
`It is not known whether Precedex is excreted in human milk.
`
`Nursing Mothers
`and delivery including cesarean section deliveries.
`studied. Therefore, Precedex is not recommended during labor
`The safety of Precedex during labor and delivery has not been
`
`Labor and Delivery
`potential benefits justify the potential risk to the fetus.
`women. Precedex® should be used during pregnancy only if the
`There are no adequate and well-controlled studies in pregnant
`
`Pregnancy
`Populations1
`Dosing in Special Patient
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`19
`
`· 0
`®Precedex®
`
`(deXJredetomicile OCI ij!ctioo)
`
`Please see enclosed full Prescribing Information.
`
`18
`
`oct.%1ir
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`diazepam.1
`administered with the following drugs: amphotericin B,
`Precedex has been shown to be INCOMPATIBLE when
`
`for a complete list.1
`of additional drugs. Please see full Prescribing Information
`Ringer's solution. Precedex is also compatible with a number
`dextrose in water, 0.9% sodium chloride in water, lactated
`administered with the following intravenous fluids: 5%
`Precedex has been shown to be COMPATIBLE when
`
`Compatibility
`
`4. Final concentration is 4 mcg/ml.
`
`3. Shake gently to mix well.
`
`2. Add to 48 ml of 0.9% sodium chloride injection
`
`to a total of 50 ml.
`
`1. Withdraw 2 ml of Precedex.
`
`To prepare the infusion1:
`whether for the loading dose or maintenance infusion.1
`prior to administration. Preparation of solutions is the same
`Precedex should be diluted in 0.9% sodium chloride solution
`
`Precedex®
`How to Reconstitute
`
`0
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`
`21
`
`tf (dexmedetomidi1e HCitljectioo)
`{]'\) Precedex~
`
`Please see enclosed full Prescribing Information.
`
`20
`
`hypnotics or opioid analgesics, a loading dose may not be necessary.
`may be required. In patients already sedated with other anesthetics, sedatives,
`and midazolam. A decrease in the dosage of Precedex or the concomitant agent
`have confirmed these effects with sevoflurane, isoflurane, propofol, alfentanil
`can enhance the pharmacodynamic effects of these agents. Specific studies
`·coa<tninistration of Precedex with anesthetics, sedatives, hypnotics and opioids
`
`is secured
`until endotracheal tube
`
`• Followed by 0.7 mcg/kg/hr
`
`10 minutes
`1 meg/kg over
`
`intubation
`Awake fiberoptic
`
`should be considered
`maintenance dosage
`
`• A reduction in
`
`considered
`should be
`A dose reduction
`
`or renal function
`impaired hepatic
`Patients with
`
`should be considered
`maintenance dosage
`
`• A reduction in
`
`targeted level of sedation
`be adjusted to achieve
`• Rate of infusion should
`
`0.2-1 mcg/kg/hr
`with doses from
`• Titrate to effect
`
`0.6 mcg/kg/hr
`
`• Followed by
`
`10 minutes
`0.5 meg/kg over
`
`Patients over 65 yrs
`
`suitable
`10 minutes may be
`0.5 meg/kg over
`
`10 minutes*
`1 meg/kg over
`
`(e.g., ophthalmic)
`procedures
`Less invasive
`
`and procedures
`Adult patients
`
`• Precedex should be administered using a controlled
`
`infusion device (IV pump ).1
`
`• Precedex is not indicated for infusions lasting longer
`
`• Precedex dosing should be individualized and titrated
`
`to the desired clinical effect. 1
`
`than 24 hours.1
`
`-Final concentration is 4 mcg/ml.
`-Shake gently to mix well.
`
`to a total of 50 ml.
`-Add to 48 ml of 0.9% sodium chloride injection
`-Withdraw 2 ml of Precedex.
`infusion. To prepare the infusion1
`is the same whether for the loading dose or maintenance
`solution prior to administration. Preparation of solutions
`
`:
`
`• Precedex® should be diluted in 0.9% sodium chloride
`
`or Other Procedures
`Sedation for Surgical
`Patients Requiring
`Dosing for Nonintubated
`
`...... ....,
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`

`
`<tJ1 Precedex~
`
`23
`(dexmedetomidi'le HCitljectioo)
`
`Please see enclosed full Prescribing Information.
`
`should be adjusted from 0.2 to 1 mcg/kg/hr to achieve the desired effect.
`
`8 INFUSION RATE (ml/hr) The rate of the maintenance infusion
`
`46.3
`45
`43.8
`42.5
`41.3
`40
`38.8
`37.5
`36.3
`35
`33.8
`32.5
`31.3
`30
`28.8
`27.5
`26.3
`25
`23.8
`22.5
`21.3
`20
`18.8
`17.5
`16.3
`15
`13.8
`12.5
`
`41.6
`40.5
`39.4
`38.3
`37.1
`36
`34.9
`33.8
`32.6
`31.5
`30.4
`29.3
`28.1
`27
`25.9
`24.8
`23.6
`22.5
`21.4
`20.3
`19.1
`18
`16.9
`15.8
`14.6
`13.5
`12.4
`11.3
`
`37
`36
`35
`34
`33
`32
`31
`30
`29
`28
`27
`26
`25
`24
`23
`22
`21
`20
`19
`18
`17
`16
`15
`14
`13
`12
`11
`10
`
`32.4
`31.5
`30.6
`29.8
`28.9
`28
`27.1
`26.3
`25.4
`24.5
`23.6
`22.8
`21.9
`21
`20.1
`19.3
`18.4
`17.5
`16.6
`15.8
`14.9
`14
`13.1
`12.3
`11.4
`10.5
`9.6
`8.8
`
`27.8
`27
`26.3
`25.5
`24.8
`24
`23.3
`22.5
`21.8
`21
`20.3
`19.5
`18.8
`18
`17.3
`16.5
`15.8
`15
`14.3
`13.5
`12.8
`12
`11.3
`10.5
`9.8
`9
`8.3
`7.5
`
`23.1
`22.5
`21.9
`21.3
`20.6
`20
`19.4
`18.8
`18.1
`17.5
`16.9
`16.3
`15.6
`15
`14.4
`13.8
`13.1
`12.5
`11.9
`11.3
`10.6
`10
`9.4
`8.8
`8.1
`7.5
`6.9
`6.3
`
`18.5
`18
`17.5
`17
`16.5
`16
`15.5
`15
`14.5
`14
`13.5
`13
`12.5
`12
`11.5
`11
`10.5
`10
`9.5
`9
`8.5
`8
`7.5
`7
`6.5
`6
`5.5
`5
`
`13.9
`13.5
`13.1
`12.8
`12.4
`12
`11.6
`11.3
`10.9
`10.5
`10.1
`9.8
`9.4
`9
`8.6
`8.3
`7.9
`7.5
`7.1
`6.8
`6.4
`6
`5.6
`5.3
`4.9
`4.5
`4.1
`3.8
`
`9.3
`9
`8.8
`8.5
`8.3
`8
`7.8
`7.5
`7.3
`7
`6.8
`6.5
`6.3
`6
`5.8
`5.5
`5.3
`5
`4.8
`4.5
`4.3
`4
`3.8
`3.5
`3.3
`3
`2.8
`2.5
`
`185
`180
`175
`170
`165
`160
`155
`150
`145
`140
`135
`130
`125
`120
`115
`110
`105
`100
`95
`90
`85
`80
`75
`70
`65
`60
`55
`50
`(kg)
`WEIG
`0
`
`Maintenance Dose14
`
`8 Find infusion rate (intersection).
`8 Find desired dose (top of column).
`0 Find patient weight (row).
`
`46.3
`45
`43.8
`42.5
`41.3
`40
`38.8
`37.5
`36.3
`35
`33.8
`32.5
`31.3
`30
`28.8
`27.5
`26.3
`25
`23.8
`22.5
`21.3
`20
`18.8
`17.5
`16.3
`15
`13.8
`12.5
`
`277.5
`270
`262.5
`255
`247.5
`240
`232.5
`225
`217.5
`210
`202.5
`195
`187.5
`180
`172.5
`165
`157.5
`150
`142.5
`135
`127.5
`120
`112.5
`105
`97.5
`90
`82.5
`75
`
`22
`
`185
`180
`175
`170
`165
`160
`155
`150
`145
`140
`135
`130
`125
`120
`115
`110
`105
`100
`95
`90
`85
`80
`75
`70
`65
`60
`55
`50
`
`opioid analgesics, a loading dose may not be necessary.1
`patients already sedated with other anesthetics, sedatives or
`of Precedex or the concomitant agent may be required. In
`propofol, alfentanil and midazolam. A decrease in the dosage
`have confirmed these effects with sevoflurane, isoflurane,
`the pharmacodynamic effects of these agents. Specific studies
`with anesthetics, sedatives, hypnotics and opioids can enhance
`of 1 meg/kg over 10 minutes. Coadministration of Precedex
`Precedex is generally initiated with a loading infusion
`
`Loading Dose14
`Based on 4 mcg/ml concentration
`
`for Procedural Sedation
`Precedex® Dosing
`
`leo
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`

`
`25
`
`tf (dexmedetomidi1e HCitljectioo)
`{]'\) Precedex~
`
`Please see enclosed full Prescribing Information.
`
`24
`
`hypnotics or opioid analgesics, a loading dose may not be necessary.
`may be required. In patients already sedated with other anesthetics, sedatives,
`and midazolam. A decrease in the dosage of Precedex or the concomitant agent
`have confirmed these effects with sevoflurane, isoflurane, propofol, alfentanil
`can enhance the pharmacodynamic effects of these agents. Specific studies
`·coacministration of Precedex with anesthetics, sedatives, hypnotics and opioids
`
`should be considered
`maintenance dosage
`
`• A reduction in
`
`should be considered
`maintenance dosage
`
`• A reduction in
`
`level of sedation
`to achieve targeted
`should be adjusted
`
`• Rate of infusion
`
`0.2-0.7 mcg/kg/hr
`with doses from
`• Titrate to effect
`
`Patients with impaired I A dose reduction
`
`considered
`should be
`
`hepatic or renal function
`
`considered
`should be
`A dose reduction
`
`Patients over 65 yrs
`
`0.4 mcg/kg/hr
`
`• Followed by
`
`10 minutes*
`1 meg/kg over
`
`Adult patients
`
`• Precedex should be administered using a controlled
`
`infusion device (IV pump).1
`
`than 24 hours.1
`• Precedex is not indicated for infusions lasting longer
`
`to the desired clinical effect.1
`• Precedex dosing should be individualized and titrated
`
`-Final concentration is 4 mcg/ml.
`-Shake gently to mix well.
`to a total of 50 ml.
`-Add to 48 ml of 0.9% sodium chloride injection
`-Withdraw 2 ml of Precedex.
`infusion. To prepare the infusion1
`is the same whether for the loading dose or maintenance
`solution prior to administration. Preparation of solutions
`
`:
`
`• Precedex® should be diluted in 0.9% sodium chloride
`
`ICU Sedation Dosing
`
`(I)U,
`ICUI
`I»UI
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`
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`
`

`
`<f) Precedex~
`
`27
`(dexrneOOtomidi'le HCil1jectioo)
`
`be adjusted from 0.2 to 0.7 mcg/kg/hr to achieve the desired effect
`
`81NFUSION RATE (ml/h r) The rate of the maintenance infusion should
`
`32.4
`31.5
`30.6
`29.8
`28.9
`28
`27.1
`26.3
`25.4
`24.5
`23.6
`22.8
`21.9
`21
`20.1
`19.3
`18.4
`17.5
`16.6
`15.8
`14.9
`14
`13.1
`12.3
`11.4
`10.5
`9.6
`8.8
`
`27.8
`27
`26.3
`25.5
`24.8
`24
`23.3
`22.5
`21.8
`21
`20.3
`19.5
`18.8
`18
`17.3
`16.5
`15.8
`15
`14.3
`13.5
`12.8
`12
`11.3
`10.5
`9.8
`9
`8.3
`7.5
`
`23.1
`22.5
`21.9
`21.3
`20.6
`20
`19.4
`18.8
`18.1
`17.5
`16.9
`16.3
`15.6
`15
`14.4
`13.8
`13.1
`12.5
`11.9
`11.3
`10.6
`10
`9.4
`8.8
`8.1
`7.5
`6.9
`6.3
`
`18.5
`18
`17.5
`17
`16.5
`16
`15.5
`15
`14.5
`14
`13.5
`13
`12.5
`12
`11.5
`11
`10.5
`10
`9.5
`9
`8.5
`8
`7.5
`7
`6.5
`6
`5.5
`5
`
`13.9
`13.5
`13.1
`12.8
`12.4
`12
`11.6
`11.3
`10.9
`10.5
`10.1
`9.8
`9.4
`9
`8.6
`8.3
`7.9
`7.5
`7.1
`6.8
`6.4
`6
`5.6
`5.3
`4.9
`4.5
`4.1
`3.8
`
`9.3
`9
`8.8
`8.5
`8.3
`8
`7.8
`7.5
`7.3
`7
`6.8
`6.5
`6.3
`6
`5.8
`5.5
`5.3
`5
`4.8
`4.5
`4.3
`4
`3.8
`3.5
`3.3
`3
`2.8
`2.5
`
`8 DOSE (mcg/kg/hr)
`
`Maintenance Dose14
`
`WEIGHT
`
`185
`180
`175
`170
`165
`160
`155
`150
`145
`140
`135
`130
`125
`120
`115
`110
`105
`100
`95
`90
`85
`80
`75
`70
`65
`60
`55
`50
`(kg)
`
`0
`
`8 Find infusion rate (intersection).
`8 Find desired dose (top of column).
`0 Find patient weight (row).
`
`---~
`
`46.3
`45
`43.8
`42.5
`41.3
`40
`38.8
`37.5
`36.3
`35
`33.8
`32.5
`31.3
`30
`28.8
`27.5
`26.3
`25
`23.8
`22.5
`21.3
`20
`18.8
`17.5
`16.3
`15
`13.8
`
`277.5
`270
`262.5
`255
`247.5
`240
`232.5
`225
`217.5
`210
`202.5
`195
`187.5
`180
`172.5
`165
`157.5
`150
`142.5
`135
`127.5
`120
`112.5
`105
`97.5
`90
`82.5
`
`----
`
`26
`
`185
`180
`175
`170
`165
`160
`155
`150
`145
`140
`135
`130
`125
`120
`115
`110
`105
`100
`95
`90
`85
`80
`75
`70
`65
`60
`55
`
`analgesics, a loading dose may not be necessary.1
`already sedated with other anesthetics, sedatives or opioid
`Precedex or the concomitant agent may be required. In patients
`propofol, alfentanil and midazolam. A decrease in the dosage of
`have confirmed these effects with sevoflurane, isoflurane,
`the pharmacodynamic effects of these agents. Specific studies
`anesthetics, sedatives, hypnotics