For intravenous administration

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

2 

24  

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1 

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

2 

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

3 

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

4 

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

2

 basis).  The 

5 

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

6 

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

7 

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

8 

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

9 

clearly needed. 

10 

Labor and Delivery 

11 

DIPRIVAN Injectable Emulsion is not recommended for obstetrics, including cesarean 

12 

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

13 

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

14 

associated with neonatal depression. 

15 

Nursing Mothers 

16 

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

17 

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

18 

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

19 

Pediatric Use 

20 

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

21 

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

22 

anesthesia aged 2 months and older. 

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

2 

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

3 

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

4 

In pediatric patients, administration of fentanyl concomitantly with DIPRIVAN 

5 

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

6 

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

7 

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

8 

effectiveness have not been established. 

9 

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

10 

patients with upper respiratory tract infections receiving DIPRIVAN Injectable Emulsion for 

11 

ICU sedation. 

12 

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

13 

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

14 

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

15 

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

16 

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

17 

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

18 

CLINICAL PHARMACOLOGY, Pharmacokinetics, Pediatric Patients and DOSAGE 

19 

AND ADMINISTRATION). 

20 

In pediatric patients, abrupt discontinuation of DIPRIVAN Injectable Emulsion 

21 

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

22 

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

23 

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

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Geriatric Use 

2 

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

3 

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

4 

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

5 

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

6 

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

7 

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

8 

for subjects greater than 60 years of age. 

9 

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

10 

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

11 

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

12 

undesirable cardiorespiratory depression including hypotension, apnea, airway obstruction, 

13 

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

14 

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

15 

or IV Patients and CLINICAL PHARMACOLOGY, Geriatrics). 

16 

ADVERSE REACTIONS: 

17 

General 

18 

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

19 

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

20 

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

21 

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

22 

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

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2 

3 

4 

5 

6 

7 

8 

9 

10 

11 

12 

13 

14 

15 

16 

17 

18 

19 

20 

21 

22 

23 

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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8 

1 

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

2 

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

3 

presence of concomitant disease and concomitant therapy made the causal relationship 

4 

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

5 

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

6 

7 

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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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 

30 

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2 

1 

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 

1 

DRUG ABUSE AND DEPENDENCE: 

2 

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

3 

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

4 

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

5 

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

6 

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

7 

accounting procedures as appropriate to the clinical setting. 

8 

OVERDOSAGE: 

9 

If overdosage occurs, DIPRIVAN Injectable Emulsion administration should be discontinued 

10 

immediately.  Overdosage is likely to cause cardiorespiratory depression.  Respiratory 

11 

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

12 

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

13 

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

14 

DOSAGE AND ADMINISTRATION: 

15 

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

16 

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

17 

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

18 

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

19 

dose adjustments to allow for and assess the clinical effects. 

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Reference ID: 3520825 

1 

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

2 

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

3 

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

4 

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

5 

When administering DIPRIVAN Injectable Emulsion by infusion, syringe or 

6 

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

7 

DIPRIVAN Injectable Emulsion to patients undergoing magnetic resonance imaging, metered 

8 

control devices may be utilized if mechanical pumps are impractical. 

9 

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

10 

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

11 

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

12 

Injectable Emulsion. 

13 

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

14 

combined with a variable rate DIPRIVAN Injectable Emulsion infusion to provide 

15 

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

16 

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

17 

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

18 

anesthesia. 

19 

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

20 

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

21 

administration of DIPRIVAN Injectable Emulsion at rates higher than are clinically 

22 

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

23 

maintenance in order to optimize recovery times. 

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

2 

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

3 

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

4 

propofol injection maintenance infusion rate and therapeutic blood concentrations when 

5 

compared to non-narcotic (lorazepam) premedication. 

6 

Induction of General Anesthesia 

7 

Adult Patients 

8 

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

9 

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

10 

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

11 

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

12 

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

13 

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

14 

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

15 

Injectable Emulsion. 

16 

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

17 

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

18 

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

19 

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

20 

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

21 

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

22 

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

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1 

2 

3 

4 

5 

6 

7 

8 

9 

10 

11 

12 

13 

14 

15 

16 

17 

18 

19 

20 

21 

22 

23 

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

desaturation (see DOSAGE AND ADMINISTRATION).