For intravenous administration



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Cardiac Anesthesia 

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DIPRIVAN Injectable Emulsion was evaluated in clinical trials involving patients undergoing 

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coronary artery bypass graft (CABG). 

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In post-CABG (coronary artery bypass graft) patients, the maintenance rate of 

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propofol administration was usually low (median 11 mcg/kg/min) due to the intraoperative 

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administration of high opioid doses.  Patients receiving DIPRIVAN Injectable Emulsion 

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required 35% less nitroprusside than midazolam patients.  During initiation of sedation in 

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post-CABG patients, a 15% to 20% decrease in blood pressure was seen in the first 60 

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Reference ID: 3520825 

minutes.  It was not possible to determine cardiovascular effects in patients with severely 

compromised ventricular function.   





INDICATIONS AND USAGE: 

DIPRIVAN Injectable Emulsion is an IV sedative-hypnotic agent that can be used as 



described in the table below. 



Table 3.  Indications for DIPRIVAN Injectable Emulsion 



Indication Approved 

Patient 

Population 

Initiation and maintenance of Monitored 

Anesthesia Care (MAC) sedation 

Adults only 

Combined sedation and regional anesthesia Adults 

only 


(see 

PRECAUTIONS

Induction of General Anesthesia 

Patients ≥ 3 years of age 

Maintenance of General Anesthesia 

Patients ≥ 2 months of age 

Intensive Care Unit (ICU) sedation of intubated, 

mechanically ventilated patients 

Adults only 



Safety, effectiveness and dosing guidelines for DIPRIVAN Injectable Emulsion have 



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not been established for MAC Sedation in the pediatric population; therefore, it is not 

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recommended for this use (see PRECAUTIONS,_Pediatric_Use'>PRECAUTIONS, Pediatric Use). 



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DIPRIVAN Injectable Emulsion is not recommended for induction of anesthesia 

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below the age of 3 years or for maintenance of anesthesia below the age of 2 months because 



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its safety and effectiveness have not been established in those populations. 

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In the Intensive Care Unit (ICU), DIPRIVAN Injectable Emulsion can be 



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administered to intubated, mechanically ventilated adult patients to provide continuous 

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sedation and control of stress responses only by persons skilled in the medical management of 



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critically ill patients and trained in cardiovascular resuscitation and airway management. 

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Reference ID: 3520825 



DIPRIVAN Injectable Emulsion is not indicated for use in Pediatric ICU sedation 

since the safety of this regimen has not been established (see PRECAUTIONS, Pediatric 





Use). 

DIPRIVAN Injectable Emulsion is not recommended for obstetrics, including 



Cesarean section deliveries.  DIPRIVAN Injectable Emulsion crosses the placenta, and as 

with other general anesthetic agents, the administration of DIPRIVAN Injectable Emulsion 



may be associated with neonatal depression (see PRECAUTIONS). 

DIPRIVAN Injectable Emulsion is not recommended for use in nursing mothers 



because propofol has been reported to be excreted in human milk, and the effects of oral 

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absorption of small amounts of propofol are not known (see PRECAUTIONS). 



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CONTRAINDICATIONS: 

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DIPRIVAN Injectable Emulsion is contraindicated in patients with a known hypersensitivity 

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to propofol or any of DIPRIVAN Injectable Emulsion components. 

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DIPRIVAN Injectable Emulsion is contraindicated in patients with allergies to eggs, 

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egg products, soybeans or soy products. 

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WARNINGS: 

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Use of DIPRIVAN Injectable Emulsion has been associated with both fatal and life­

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threatening anaphylactic and anaphylactoid reactions.   

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For general anesthesia or monitored anesthesia care (MAC) sedation, DIPRIVAN 

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Injectable Emulsion should be administered only by persons trained in the administration of 

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general anesthesia and not involved in the conduct of the surgical/diagnostic procedure.  

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Sedated patients should be continuously monitored, and facilities for maintenance of a patent 

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airway, providing artificial ventilation, administering supplemental oxygen, and instituting 

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Reference ID: 3520825 







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cardiovascular resuscitation must be immediately available.  Patients should be continuously 

monitored for early signs of hypotension, apnea, airway obstruction, and/or oxygen 

desaturation.  These cardiorespiratory effects are more likely to occur following rapid bolus 

administration, especially in the elderly, debilitated, or ASA-PS III or IV patients. 

For sedation of intubated, mechanically ventilated patients in the Intensive Care Unit 

(ICU), DIPRIVAN Injectable Emulsion should be administered only by persons skilled in the 

management of critically ill patients and trained in cardiovascular resuscitation and airway 

management. 

Use of DIPRIVAN Injectable Emulsion infusions for both adult and pediatric 

ICU sedation has been associated with a constellation of metabolic derangements and 

organ system failures, referred to as Propofol Infusion Syndrome, that have resulted in 

death.  The syndrome is characterized by severe metabolic acidosis, hyperkalemia, 

lipemia, rhabdomyolysis, hepatomegaly, renal failure, ECG changes* and/or cardiac 

failure.  The following appear to be major risk factors for the development of these 

events: decreased oxygen delivery to tissues; serious neurological injury and/or sepsis; 

high dosages of one or more of the following pharmacological agents: vasoconstrictors, 

steroids, inotropes and/or prolonged, high-dose infusions of propofol (> 5 mg/kg/h for > 

48h).  The syndrome has also been reported following large-dose, short-term infusions 

during surgical anesthesia.  In the setting of prolonged need for sedation, increasing 

propofol dose requirements to maintain a constant level of sedation, or onset of 

metabolic acidosis during administration of a propofol infusion, consideration should be 

given to using alternative means of sedation. 

*Coved ST segment elevation (similar to ECG changes of the Brugada syndrome). 

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Reference ID: 3520825 

Abrupt discontinuation of DIPRIVAN Injectable Emulsion prior to weaning or for 

daily evaluation of sedation levels should be avoided.  This may result in rapid awakening 



with associated anxiety, agitation, and resistance to mechanical ventilation.  Infusions of 

DIPRIVAN Injectable Emulsion should be adjusted to maintain a light level of sedation 



through the weaning process or evaluation of sedation level (see PRECAUTIONS). 

DIPRIVAN Injectable Emulsion should not be coadministered through the same IV 



catheter with blood or plasma because compatibility has not been established.  In vitro tests 

have shown that aggregates of the globular component of the emulsion vehicle have occurred 



with blood/plasma/serum from humans and animals.  The clinical significance of these 

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findings is not known. 



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There have been reports in which failure to use aseptic technique when handling 

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Diprivan Injectable Emulsion was associated with microbial contamination of the 

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product and with fever, infection, sepsis, other life-threatening illness, and death.  Do 

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not use if contamination is suspected.  Discard unused drug product as directed within 

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the required time limits (see DOSAGE AND ADMINISTRATIONHandling 

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Procedures). 

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There have been reports, in the literature and other public sources, of the 

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transmission of bloodborne pathogens (such as Hepatitis B, Hepatitis C, and HIV) from 

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unsafe injection practices, and use of propofol vials intended for single use on multiple 

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persons.  DIPRIVAN Injectable Emulsion vial is never to be accessed more than once or 

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used on more than one person. 

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Reference ID: 3520825 



PRECAUTIONS: 



General 



Adult and Pediatric Patients 

A lower induction dose and a slower maintenance rate of administration should be used in 



elderly, debilitated, or ASA-PS III or IV patients (see DOSAGE AND 



ADMINISTRATION).  Patients should be continuously monitored for early signs of 

hypotension and/or bradycardia.  Apnea requiring ventilatory support often occurs during 



induction and may persist for more than 60 seconds.  DIPRIVAN Injectable Emulsion use 

requires caution when administered to patients with disorders of lipid metabolism such as 



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primary hyperlipoproteinemia, diabetic hyperlipemia, and pancreatitis. 

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Very rarely the use of DIPRIVAN Injectable Emulsion may be associated with the 



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development of a period of postoperative unconsciousness which may be accompanied by an 

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increase in muscle tone.  This may or may not be preceded by a brief period of wakefulness.  



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Recovery is spontaneous. 

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When DIPRIVAN Injectable Emulsion is administered to an epileptic patient, there is 



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a risk of seizure during the recovery phase. 

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Attention should be paid to minimize pain on administration of DIPRIVAN Injectable 



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Emulsion.  Transient local pain can be minimized if the larger veins of the forearm or 

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antecubital fossa are used.  Pain during intravenous injection may also be reduced by prior 



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injection of IV lidocaine (1 mL of a 1% solution).  Pain on injection occurred frequently in 

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pediatric patients (45%) when a small vein of the hand was utilized without lidocaine 



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pretreatment.  With lidocaine pretreatment or when antecubital veins were utilized, pain was 

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minimal (incidence less than 10%) and well-tolerated.  There have been reports in the 



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Reference ID: 3520825 



literature indicating that the addition of lidocaine to DIPRIVAN Injectable Emulsion in 

quantities greater than 20 mg lidocaine/200 mg DIPRIVAN Injectable Emulsion results in 



instability of the emulsion which is associated with increases in globule sizes over time and 

(in rat studies) a reduction in anesthetic potency.  Therefore, it is recommended that lidocaine 



be administered prior to DIPRIVAN Injectable Emulsion administration or that it be added to 

DIPRIVAN Injectable Emulsion immediately before administration and in quantities not 



exceeding 20 mg lidocaine/200 mg DIPRIVAN. 

Venous sequelae, i.e., phlebitis or thrombosis, have been reported rarely (<1%).  In 



two clinical studies using dedicated intravenous catheters, no instances of venous sequelae 

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were observed up to 14 days following induction. 



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Intra-arterial injection in animals did not induce local tissue effects.  Accidental intra­

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arterial injection has been reported in patients, and, other than pain, there were no major 



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sequelae. 

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Intentional injection into subcutaneous or perivascular tissues of animals caused 



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minimal tissue reaction.  During the post-marketing period, there have been rare reports of 

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local pain, swelling, blisters, and/or tissue necrosis following accidental extravasation of 



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DIPRIVAN Injectable Emulsion. 

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Perioperative myoclonia, rarely including convulsions and opisthotonos, has occurred 



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in association with DIPRIVAN Injectable Emulsion administration. 

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Clinical features of anaphylaxis, including angioedema, bronchospasm, erythema, and 



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hypotension, occur rarely following DIPRIVAN Injectable Emulsion administration. 

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There have been rare reports of pulmonary edema in temporal relationship to the 



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administration of DIPRIVAN Injectable Emulsion, although a causal relationship is unknown. 

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Reference ID: 3520825 



Rarely, cases of unexplained postoperative pancreatitis (requiring hospital admission) 

have been reported after anesthesia in which DIPRIVAN Injectable Emulsion was one of the 



induction agents used.  Due to a variety of confounding factors in these cases, including 

concomitant medications, a causal relationship to DIPRIVAN Injectable Emulsion is unclear. 



DIPRIVAN Injectable Emulsion has no vagolytic activity.  Reports of bradycardia, 

asystole, and rarely, cardiac arrest have been associated with DIPRIVAN Injectable 



Emulsion.  Pediatric patients are susceptible to this effect, particularly when fentanyl is given 

concomitantly.  The intravenous administration of anticholinergic agents (e.g., atropine or 



glycopyrrolate) should be considered to modify potential increases in vagal tone due to 

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concomitant agents (e.g., succinylcholine) or surgical stimuli.  



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Intensive Care Unit Sedation 

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Adult Patients 

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(See WARNINGS and DOSAGE AND ADMINISTRATION, Handling Procedures.)  The 

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administration of DIPRIVAN Injectable Emulsion should be initiated as a continuous infusion 

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and changes in the rate of administration made slowly (>5 min) in order to minimize 

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hypotension and avoid acute overdosage (see DOSAGE AND ADMINISTRATION). 

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Patients should be monitored for early signs of significant hypotension and/or 

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cardiovascular depression, which may be profound.  These effects are responsive to 

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discontinuation of DIPRIVAN Injectable Emulsion, IV fluid administration, and/or 

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vasopressor therapy.  In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or 

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repeated) bolus administration should not be used during sedation in order to minimize 

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undesirable cardiorespiratory depression, including hypotension, apnea, airway obstruction, 

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and oxygen desaturation. 

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Reference ID: 3520825 

As with other sedative medications, there is wide interpatient variability in 

DIPRIVAN Injectable Emulsion dosage requirements, and these requirements may change 



with time. 

Failure to reduce the infusion rate in patients receiving DIPRIVAN Injectable 



Emulsion for extended periods may result in excessively high blood concentrations of the 

drug.  Thus, titration to clinical response and daily evaluation of sedation levels are important 



during use of DIPRIVAN Injectable Emulsion infusion for ICU sedation, especially when it is 

used for long durations. 



Opioids and paralytic agents should be discontinued and respiratory function 

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optimized prior to weaning patients from mechanical ventilation.  Infusions of DIPRIVAN 



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Injectable Emulsion should be adjusted to maintain a light level of sedation prior to weaning 

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patients from mechanical ventilatory support.  Throughout the weaning process, this level of 



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sedation may be maintained in the absence of respiratory depression.  Because of the rapid 

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clearance of DIPRIVAN Injectable Emulsion, abrupt discontinuation of a patient's infusion 



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may result in rapid awakening with associated anxiety, agitation, and resistance to mechanical 

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ventilation, making weaning from mechanical ventilation difficult.  It is therefore 



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recommended that administration of DIPRIVAN Injectable Emulsion be continued in order to 

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maintain a light level of sedation throughout the weaning process until 10 to 15 minutes prior 



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to extubation, at which time the infusion can be discontinued. 

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Since DIPRIVAN Injectable Emulsion is formulated in an oil-in-water emulsion, 



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elevations in serum triglycerides may occur when DIPRIVAN Injectable Emulsion is 

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administered for extended periods of time.  Patients at risk of hyperlipidemia should be 



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monitored for increases in serum triglycerides or serum turbidity.  Administration of 

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Reference ID: 3520825 



DIPRIVAN Injectable Emulsion should be adjusted if fat is being inadequately cleared from 

the body.  A reduction in the quantity of concurrently administered lipids is indicated to 



compensate for the amount of lipid infused as part of the DIPRIVAN Injectable Emulsion 

formulation; 1 mL of DIPRIVAN Injectable Emulsion contains approximately 0.1 g of fat 



(1.1 kcal). 

EDTA is a strong chelator of trace metals – including zinc.  Although with 



DIPRIVAN Injectable Emulsion there are no reports of decreased zinc levels or zinc 

deficiency-related adverse events, DIPRIVAN Injectable Emulsion should not be infused for 



longer than 5 days without providing a drug holiday to safely replace estimated or measured 

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urine zinc losses. 



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In clinical trials mean urinary zinc loss was approximately 2.5 to 3 mg/day in adult 

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patients and 1.5 to 2 mg/day in pediatric patients.  



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In patients who are predisposed to zinc deficiency, such as those with burns, diarrhea, 

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and/or major sepsis, the need for supplemental zinc should be considered during prolonged 



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therapy with DIPRIVAN Injectable Emulsion. 

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At high doses (2 to 3 grams per day), EDTA has been reported, on rare occasions, to 



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be toxic to the renal tubules.  Studies to date in patients with normal or impaired renal 

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function have not shown any alteration in renal function with DIPRIVAN Injectable Emulsion 



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containing 0.005% disodium edetate.  In patients at risk for renal impairment, urinalysis and 

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urine sediment should be checked before initiation of sedation and then be monitored on 



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alternate days during sedation. 

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The long-term administration of DIPRIVAN Injectable Emulsion to patients with 



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renal failure and/or hepatic insufficiency has not been evaluated. 

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Reference ID: 3520825 





Neurosurgical Anesthesia 

When DIPRIVAN Injectable Emulsion is used in patients with increased intracranial pressure 



or impaired cerebral circulation, significant decreases in mean arterial pressure should be 

avoided because of the resultant decreases in cerebral perfusion pressure.  To avoid 



significant hypotension and decreases in cerebral perfusion pressure, an infusion or slow 

bolus of approximately 20 mg every 10 seconds should be utilized instead of rapid, more 



frequent, and/or larger boluses of DIPRIVAN Injectable Emulsion.  Slower induction, titrated 

to clinical responses, will generally result in reduced induction dosage requirements (1 to  



2 mg/kg).  When increased ICP is suspected, hyperventilation and hypocarbia should 

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accompany the administration of DIPRIVAN Injectable Emulsion (see DOSAGE AND 



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ADMINISTRATION). 

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Cardiac Anesthesia 

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Slower rates of administration should be utilized in premedicated patients, geriatric patients, 

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patients with recent fluid shifts, and patients who are hemodynamically unstable.  Fluid 

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deficits should be corrected prior to administration of DIPRIVAN Injectable Emulsion.  In 

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those patients where additional fluid therapy may be contraindicated, other measures, e.g., 

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elevation of lower extremities, or use of pressor agents, may be useful to offset the 

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hypotension which is associated with the induction of anesthesia with DIPRIVAN Injectable 

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Emulsion. 

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Information for Patients 

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Patients should be advised that performance of activities requiring mental alertness, such as 

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operating a motor vehicle, or hazardous machinery or signing legal documents may be 

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impaired for some time after general anesthesia or sedation.   

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Reference ID: 3520825 



Drug Interactions 

The induction dose requirements of DIPRIVAN Injectable Emulsion may be reduced in 



patients with intramuscular or intravenous premedication, particularly with narcotics (e.g., 

morphine, meperidine, and fentanyl, etc.) and combinations of opioids and sedatives (e.g., 



benzodiazepines, barbiturates, chloral hydrate, droperidol, etc.).  These agents may increase 

the anesthetic or sedative effects of DIPRIVAN Injectable Emulsion and may also result in 



more pronounced decreases in systolic, diastolic, and mean arterial pressures and cardiac 

output. 


During maintenance of anesthesia or sedation, the rate of DIPRIVAN Injectable 

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Emulsion administration should be adjusted according to the desired level of anesthesia or 



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sedation and may be reduced in the presence of supplemental analgesic agents (e.g., nitrous 

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oxide or opioids).  The concurrent administration of potent inhalational agents (e.g., 



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isoflurane, enflurane, and halothane) during maintenance with DIPRIVAN Injectable 

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Emulsion has not been extensively evaluated.  These inhalational agents can also be expected 



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to increase the anesthetic or sedative and cardiorespiratory effects of DIPRIVAN Injectable 

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Emulsion. 



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DIPRIVAN Injectable Emulsion does not cause a clinically significant change in 

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onset, intensity or duration of action of the commonly used neuromuscular blocking agents 



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(e.g., succinylcholine and nondepolarizing muscle relaxants).   

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No significant adverse interactions with commonly used premedications or drugs used 



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during anesthesia or sedation (including a range of muscle relaxants, inhalational agents, 

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analgesic agents, and local anesthetic agents) have been observed in adults.  In pediatric 



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Reference ID: 3520825 









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patients, administration of fentanyl concomitantly with DIPRIVAN Injectable Emulsion may 

result in serious bradycardia. 



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