For intravenous administration



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Carcinogenesis 

Long-term studies in animals have not been performed to evaluate the carcinogenic potential 

of propofol. 

Mutagenesis 

Propofol was not mutagenic in the in vitro bacterial reverse mutation assay (Ames test) using 



Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and TA1538.  Propofol was 

not mutagenic in either the gene mutation/gene conversion test using Saccharomyces 



cerevisiae, or in vitro cytogenetic studies in Chinese hamsters.  In the in vivo mouse 

micronucleus assay with Chinese Hamsters propofol administration did not produce 

chromosome aberrations. 

Impairment of Fertility 

Female Wistar rats were administered either 0, 10, or 15 mg/kg/day propofol intravenously 

from 2 weeks before pregnancy to day 7 of gestation did not show impaired fertility.  Male 

fertility in rats was not affected in a dominant lethal study at intravenous doses up to  

15 mg/kg/day for 5 days. 

Pregnancy 

Teratogenic Effects 

Pregnancy Category B 

Reproduction studies have been performed in rats and rabbits at intravenous doses of 15 

mg/kg/day (approximately equivalent to the recommended human induction dose on a mg/m

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Reference ID: 3520825 

basis) and have revealed no evidence of impaired fertility or harm to the fetus due to propofol.  

Propofol, however, has been shown to cause maternal deaths in rats and rabbits and decreased 



pup survival during the lactating period in dams treated with 15 mg/kg/day (approximately 

equivalent to the recommended human induction dose on a mg/m



2

 basis).  The 

pharmacological activity (anesthesia) of the drug on the mother is probably responsible for the 



adverse effects seen in the offspring.  There are, however, no adequate and well-controlled 

studies in pregnant women.  Because animal reproduction studies are not always predictive of 



human responses, DIPRIVAN Injectable Emulsion should be used during pregnancy only if 

clearly needed. 



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Labor and Delivery 

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DIPRIVAN Injectable Emulsion is not recommended for obstetrics, including cesarean 

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

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general anesthetic agents, the administration of DIPRIVAN Injectable Emulsion may be 

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associated with neonatal depression. 

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Nursing Mothers 

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DIPRIVAN Injectable Emulsion is not recommended for use in nursing mothers because 

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DIPRIVAN Injectable Emulsion has been reported to be excreted in human milk and the 

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effects of oral absorption of small amounts of propofol are not known. 

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Pediatric Use 

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The safety and effectiveness of DIPRIVAN Injectable Emulsion have been established for 

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induction of anesthesia in pediatric patients aged 3 years and older and for the maintenance of 

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anesthesia aged 2 months and older. 

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Reference ID: 3520825 

DIPRIVAN Injectable Emulsion is not recommended for the induction of anesthesia in 

patients younger than 3 years of age and for the maintenance of anesthesia in patients younger 



than 2 months of age as safety and effectiveness have not been established. 

In pediatric patients, administration of fentanyl concomitantly with DIPRIVAN 



Injectable Emulsion may result in serious bradycardia (see PRECAUTIONS, General). 

DIPRIVAN Injectable Emulsion is not indicated for use in pediatric patients for ICU 



sedation or for MAC sedation for surgical, nonsurgical or diagnostic procedures as safety and 

effectiveness have not been established. 



There have been anecdotal reports of serious adverse events and death in pediatric 

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patients with upper respiratory tract infections receiving DIPRIVAN Injectable Emulsion for 



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ICU sedation. 

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In one multicenter clinical trial of ICU sedation in critically ill pediatric patients that 



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excluded patients with upper respiratory tract infections, the incidence of mortality observed 

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in patients who received DIPRIVAN Injectable Emulsion (n=222) was 9%, while that for 



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patients who received standard sedative agents (n=105) was 4%.  While causality has not been 

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established, DIPRIVAN Injectable Emulsion is not indicated for sedation in pediatric patients 



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until further studies have been performed to document its safety in that population (see 

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CLINICAL PHARMACOLOGY, PharmacokineticsPediatric Patients and DOSAGE 

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AND ADMINISTRATION). 

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In pediatric patients, abrupt discontinuation of DIPRIVAN Injectable Emulsion 

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following prolonged infusion may result in flushing of the hands and feet, agitation, 

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tremulousness and hyperirritability.  Increased incidences of bradycardia (5%), agitation 

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(4%), and jitteriness (9%) have also been observed. 

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Reference ID: 3520825 



Geriatric Use 

The effect of age on induction dose requirements for propofol was assessed in an open-label 



study involving 211 unpremedicated patients with approximately 30 patients in each decade 

between the ages of 16 and 80.  The average dose to induce anesthesia was calculated for 



patients up to 54 years of age and for patients 55 years of age or older.  The average dose to 

induce anesthesia in patients up to 54 years of age was 1.99 mg/kg and in patients above 54 it 



was 1.66 mg/kg.  Subsequent clinical studies have demonstrated lower dosing requirements 

for subjects greater than 60 years of age. 



A lower induction dose and a slower maintenance rate of administration of 

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DIPRIVAN Injectable Emulsion should be used in elderly patients.  In this group of patients, 



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rapid (single or repeated) bolus administration should not be used in order to minimize 

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undesirable cardiorespiratory depression including hypotension, apnea, airway obstruction, 



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and/or oxygen desaturation.  All dosing should be titrated according to patient condition and 

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response (see DOSAGE AND ADMINISTRATION, Elderly, Debilitated or ASA-PS III 



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or IV Patients and CLINICAL PHARMACOLOGY, Geriatrics). 

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ADVERSE REACTIONS: 

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General 

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Adverse event information is derived from controlled clinical trials and worldwide marketing 

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experience.  In the description below, rates of the more common events represent 

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US/Canadian clinical study results.  Less frequent events are also derived from publications 

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and marketing experience in over 8 million patients; there are insufficient data to support an 

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accurate estimate of their incidence rates.  These studies were conducted using a variety of 

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Reference ID: 3520825 







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premedicants, varying lengths of surgical/diagnostic procedures, and various other 

anesthetic/sedative agents.  Most adverse events were mild and transient. 



Anesthesia and MAC Sedation in Adults 

The following estimates of adverse events for DIPRIVAN Injectable Emulsion include data 

from clinical trials in general anesthesia/MAC sedation (N=2889 adult patients).  The adverse 

events listed below as probably causally related are those events in which the actual incidence 

rate in patients treated with DIPRIVAN Injectable Emulsion was greater than the comparator 

incidence rate in these trials.  Therefore, incidence rates for anesthesia and MAC sedation in 

adults generally represent estimates of the percentage of clinical trial patients which appeared 

to have probable causal relationship. 

The adverse experience profile from reports of 150 patients in the MAC sedation 

clinical trials is similar to the profile established with DIPRIVAN Injectable Emulsion during 

anesthesia (see below).  During MAC sedation clinical trials, significant respiratory events 

included cough, upper airway obstruction, apnea, hypoventilation, and dyspnea.  



Anesthesia in Pediatric Patients 

Generally the adverse experience profile from reports of 506 DIPRIVAN Injectable Emulsion 

pediatric patients from 6 days through 16 years of age in the US/Canadian anesthesia clinical 

trials is similar to the profile established with DIPRIVAN Injectable Emulsion during 

anesthesia in adults (see Pediatric percentages [Peds %] below).  Although not reported as an 

adverse event in clinical trials, apnea is frequently observed in pediatric patients. 



ICU Sedation in Adults 

The following estimates of adverse events include data from clinical trials in ICU sedation 

(N=159 adult patients).  Probably related incidence rates for ICU sedation were determined by 

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Reference ID: 3520825 

individual case report form review.  Probable causality was based upon an apparent dose 



response relationship and/or positive responses to rechallenge.  In many instances the 

presence of concomitant disease and concomitant therapy made the causal relationship 



unknown.  Therefore, incidence rates for ICU sedation generally represent estimates of the 

percentage of clinical trial patients which appeared to have a probable causal relationship. 





Incidence greater than 1% - Probably Causally Related 

Cardiovascular: 

Anesthesia/MAC Sedation 

ICU Sedation 

Bradycardia 

Bradycardia 

 Arrhythmia 

[Peds: 

1.2%] 


Tachycardia Nodal [Peds: 1.6%] 

Hypotension* [Peds: 17%] 

(see also CLINICAL PHARMACOLOGY

Decreased Cardiac Output 

Hypertension [Peds: 8%] 

Hypotension 26% 

Central Nervous System:  Movement* [Peds: 17%] 

Injection Site: 

Burning/Stinging or Pain, 

17.6% [Peds: 10%] 

Metabolic/Nutritional: 

Hyperlipemia* 

Respiratory: Apnea 

(see also CLINICAL PHARMACOLOGY

Respiratory Acidosis During 

Weaning* 

Skin and Appendages: 

Rash [Peds: 5%] 

Pruritus [Peds: 2%] 

Events without an * or % had an incidence of 1% to 3% 

*Incidence of events 3% to 10% 

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Reference ID: 3520825 



Incidence less than 1% - Probably Causally Related 

Body as a Whole: 



 Anesthesia/MAC Sedation 

ICU Sedation 

Anaphylaxis/Anaphylactoid Reaction 

 Perinatal 

Disorder 

 [Tachycardia] 

 [Bigeminy]

 [Bradycardia]

 [Premature 

Ventricular 

Contractions]

 [Hemorrhage] 

 [ECG 


Abnormal] 

 [Arrhythmia 

Atrial] 

 [Fever] 

 [Extremities 

Pain]


 [Anticholinergic 

Syndrome] 

Cardiovascular: Premature 

Atrial 


Contractions 

Syncope 


Central Nervous System:  Hypertonia/Dystonia, Paresthesia 

Agitation 

Digestive: [Hypersalivation] 

 [Nausea] 

Hemic/Lymphatic:  

[Leukocytosis] 

Injection Site: 

[Phlebitis] 

 [Pruritus] 

Metabolic: [Hypomagnesemia] 

Musculoskeletal: Myalgia 

Nervous: [Dizziness] 

[Agitation] 

[Chills] 

[Somnolence] 

[Delirium] 

Respiratory: Wheezing 

[Cough] 


[Laryngospasm] 

[Hypoxia] 

Decreased Lung Function 

Skin and Appendages:  

Flushing, Pruritus 

Special Senses: 

Amblyopia 

[Vision Abnormal] 

Urogenital: 

Cloudy Urine 

Green Urine 

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Reference ID: 3520825 





Incidence less than 1% - Causal Relationship Unknown 

Anesthesia/MAC Sedation 

ICU Sedation 

Body as a Whole: 

Asthenia, Awareness, Chest Pain

Extremities Pain, Fever, Increased 

Drug Effect, Neck Rigidity/Stiffness, 

Trunk Pain 

Fever, Sepsis, Trunk Pain, Whole Body Weakness 

Cardiovascular: 

Arrhythmia, Atrial Fibrillation, 

Atrioventricular Heart Block, 

Bigeminy, Bleeding, Bundle Branch 

Arrhythmia, Atrial Fibrillation, Bigeminy, Cardiac 

Arrest, Extrasystole, Right Heart Failure, Ventricular 

Tachycardia 

Block, Cardiac Arrest, ECG Abnormal,  

Edema, Extrasystole, Heart Block,  

Hypertension, Myocardial  

Infarction, Myocardial Ischemia,  

Premature Ventricular Contractions, 

ST Segment Depression,  

Supraventricular Tachycardia, 

Tachycardia, Ventricular Fibrillation  

Central Nervous System:  Abnormal Dreams, Agitation, 

Chills/Shivering, Intracranial Hypertension

Amorous Behavior, Anxiety, 

Seizures, Somnolence, Thinking Abnormal 

Bucking/Jerking/Thrashing,  

Chills/Shivering/Clonic/Myoclonic 

Movement, Combativeness, 

Confusion, Delirium, Depression, 

Dizziness, Emotional Lability, 

Euphoria, Fatigue, Hallucinations, 

Headache, Hypotonia, Hysteria, 

Insomnia, Moaning, Neuropathy, 

Opisthotonos, Rigidity, Seizures, 

Somnolence, Tremor, Twitching 

Digestive: 

Cramping, Diarrhea, Dry Mouth, 

Ileus, Liver Function Abnormal 

Enlarged Parotid, Nausea, Swallowing, 

Vomiting 

Hematologic/Lymphatic:  Coagulation Disorder, Leukocytosis 

Injection Site: 

Hives/Itching, Phlebitis, 

Redness/Discoloration 

Metabolic/Nutritional: Hyperkalemia, 

Hyperlipemia 

BUN Increased, Creatinine Increased, Dehydration, 

Hyperglycemia, Metabolic Acidosis, Osmolality 

Increased 

Respiratory: 

Bronchospasm, Burning in Throat, 

Hypoxia 

Cough, Dyspnea, Hiccough, 

Hyperventilation, Hypoventilation, 

Hypoxia, Laryngospasm, Pharyngitis, 

Sneezing, Tachypnea, Upper Airway 

Obstruction 

Skin and Appendages: 

Conjunctival Hyperemia, Diaphoresis,  Rash 

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Reference ID: 3520825 



Urticaria 

Special Senses: 

Diplopia, Ear Pain, Eye Pain, 

Nystagmus, Taste Perversion

Tinnitus 

Urogenital: 

Oliguria, Urine Retention 

Kidney Failure 



DRUG ABUSE AND DEPENDENCE: 

There are reports of the abuse of propofol for recreational and other improper purposes, which 



have resulted in fatalities and other injuries.  Instances of self-administration of DIPRIVAN 

Injectable Emulsion by health care professionals have also been reported, which have resulted 



in fatalities and other injuries.  Inventories of DIPRIVAN Injectable Emulsion should be 

stored and managed to prevent the risk of diversion, including restriction of access and 



accounting procedures as appropriate to the clinical setting. 



OVERDOSAGE: 

If overdosage occurs, DIPRIVAN Injectable Emulsion administration should be discontinued 



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immediately.  Overdosage is likely to cause cardiorespiratory depression.  Respiratory 

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depression should be treated by artificial ventilation with oxygen.  Cardiovascular depression 



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may require repositioning of the patient by raising the patient's legs, increasing the flow rate 

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of intravenous fluids, and administering pressor agents and/or anticholinergic agents. 



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DOSAGE AND ADMINISTRATION: 

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Propofol blood concentrations at steady-state are generally proportional to infusion rates, 

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especially in individual patients.  Undesirable effects such as cardiorespiratory depression are 

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likely to occur at higher blood concentrations which result from bolus dosing or rapid 

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increases in the infusion rate.  An adequate interval (3 to 5 minutes) must be allowed between 

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dose adjustments to allow for and assess the clinical effects. 

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Reference ID: 3520825 

Shake well before use.  Do not use if there is evidence of excessive creaming or 

aggregation, if large droplets are visible, or if there are other forms of phase separation 



indicating that the stability of the product has been compromised.  Slight creaming, which 

should disappear after shaking, may be visible upon prolonged standing. 



When administering DIPRIVAN Injectable Emulsion by infusion, syringe or 

volumetric pumps are recommended to provide controlled infusion rates.  When infusing 



DIPRIVAN Injectable Emulsion to patients undergoing magnetic resonance imaging, metered 

control devices may be utilized if mechanical pumps are impractical. 



Changes in vital signs indicating a stress response to surgical stimulation or the 

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emergence from anesthesia may be controlled by the administration of 25 mg (2.5 mL) to  



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50 mg (5 mL) incremental boluses and/or by increasing the infusion rate of DIPRIVAN 

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Injectable Emulsion. 



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For minor surgical procedures (e.g., body surface) nitrous oxide (60% to 70%) can be 

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combined with a variable rate DIPRIVAN Injectable Emulsion infusion to provide 



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satisfactory anesthesia.  With more stimulating surgical procedures (e.g., intra-abdominal), or 

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if supplementation with nitrous oxide is not provided, administration rate(s) of DIPRIVAN 



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Injectable Emulsion and/or opioids should be increased in order to provide adequate 

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anesthesia. 



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Infusion rates should always be titrated downward in the absence of clinical signs of 

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light anesthesia until a mild response to surgical stimulation is obtained in order to avoid 



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administration of DIPRIVAN Injectable Emulsion at rates higher than are clinically 

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necessary.  Generally, rates of 50 to 100 mcg/kg/min in adults should be achieved during 



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maintenance in order to optimize recovery times. 

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Reference ID: 3520825 



Other drugs that cause CNS depression (hypnotics/sedatives, inhalational anesthetics, 

and opioids) can increase CNS depression induced by propofol.  Morphine premedication 



(0.15 mg/kg) with nitrous oxide 67% in oxygen has been shown to decrease the necessary 

propofol injection maintenance infusion rate and therapeutic blood concentrations when 



compared to non-narcotic (lorazepam) premedication. 



Induction of General Anesthesia 



Adult Patients 

Most adult patients under 55 years of age and classified as ASA-PS I or II require 2 to  



2.5 mg/kg of DIPRIVAN Injectable Emulsion for induction when unpremedicated or when 

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premedicated with oral benzodiazepines or intramuscular opioids.  For induction, DIPRIVAN 



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Injectable Emulsion should be titrated (approximately 40 mg every 10 seconds) against the 

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response of the patient until the clinical signs show the onset of anesthesia.  As with other 



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sedative-hypnotic agents, the amount of intravenous opioid and/or benzodiazepine 

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premedication will influence the response of the patient to an induction dose of DIPRIVAN 



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Injectable Emulsion. 

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Elderly, Debilitated, or ASA-PS III or IV Patients 

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It is important to be familiar and experienced with the intravenous use of DIPRIVAN 

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Injectable Emulsion before treating elderly, debilitated, or ASA-PS III or IV patients.  Due to 

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the reduced clearance and higher blood concentrations, most of these patients require 

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approximately 1 to 1.5 mg/kg (approximately 20 mg every 10 seconds) of DIPRIVAN 

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Injectable Emulsion for induction of anesthesia according to their condition and responses.  A 

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rapid bolus should not be used, as this will increase the likelihood of undesirable 

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Reference ID: 3520825 







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cardiorespiratory depression including hypotension, apnea, airway obstruction, and/or oxygen 

desaturation (see DOSAGE AND ADMINISTRATION). 



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