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Propofol: Drug information

Propofol: Drug information
(For additional information see "Propofol: Patient drug information" and see "Propofol: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Special Alerts
Propofol-Lipuro COVID-19 Emergency Use Authorization March 2021

The FDA has issued an emergency use authorization (EUA) during the COVID-19 pandemic to permit the emergency use of the unapproved product Propofol-Lipuro 1% (propofol 10 mg/mL) emulsion for infusion. The EUA allows for Propofol-Lipuro to be distributed in the United States and administered only by a licensed health care provider in an intensive care unit (ICU) setting; Propofol-Lipuro will be used only to maintain sedation via continuous infusion in patients older than 16 years who require mechanical ventilation. Propofol-Lipuro will not be administered to pregnant women, unless there are no FDA-approved products available to maintain sedation for these patients should they require mechanical ventilation in an ICU setting; and it will be used only in accordance with the dosing regimens as detailed in the authorized Fact Sheet. Health care providers should review the Fact Sheet for Health Care Providers for key differences between products.

The Fact Sheet for Health Care Providers may be found at: https://www.fda.gov/media/146681/download

The Fact Sheet for Patients And Parent/Caregivers may be found at: https://www.fda.gov/media/146682/download

Fresenius Propoven COVID-19 Emergency Use Authorization May 2020

The FDA has issued an emergency use authorization (EUA) during the COVID-19 pandemic to permit the emergency use of the unapproved product Fresenius Propoven 2% (propofol 20 mg/mL) emulsion. The EUA allows for Fresenius Propoven to be distributed in the United States and administered only by a licensed health care provider in an intensive care unit (ICU) setting; Fresenius Propoven will be used only to maintain sedation via continuous infusion in patients older than 16 years who require mechanical ventilation. Fresenius Propoven will not be administered to pregnant women, unless there are no FDA-approved products available to maintain sedation for these patients should they require mechanical ventilation in an ICU setting, and it will be used only in accordance with the dosing regimens as detailed in the authorized Fact Sheet. Because Fresenius Propoven 2% contains double the concentration of propofol (20 mg/mL) compared to FDA-approved propofol products (10 mg/mL), there is a risk of unintentional overdose. Health care providers should review the Fact Sheet for Health Care Providers for key differences between products.

The Fact Sheet tor Health Care Providers may be found at: https://www.fda.gov/media/137889/download

The Fact Sheet for Patients And Parent/Caregivers may be found at: https://www.fda.gov/media/137890/download

Brand Names: US
  • Diprivan;
  • Fresenius Propoven;
  • Propofol-Lipuro
Brand Names: Canada
  • Diprivan;
  • Propofol-II [DSC];
  • TEVA-Propofol
Pharmacologic Category
  • General Anesthetic
Dosing: Adult

Note : The FDA has issued an emergency use authorization (EUA) during the COVID-19 pandemic to permit the emergency use of the unapproved products, Propofol-Lipuro 1% (propofol 10 mg/mL) and Fresenius Propoven 2% (propofol 20 mg/mL) emulsion. Because Fresenius Propoven 2% contains double the concentration of propofol (20 mg/mL) compared to the FDA-approved propofol products (10 mg/mL), there is a risk of unintentional overdose. Health care providers should review the Fact Sheet for Health Care Providers for key differences between products:

Propofol-Lipuro 1% Fact Sheet: https://www.fda.gov/media/146681/download

Propoven 2% Fact Sheet: https://www.fda.gov/media/137889/download

Prior to use, consult local/state regulations and institutional policies and procedures regarding administration and monitoring requirements; dosing practices may vary. For dosing in obese patients, use ideal body weight or adjusted body weight for initial weight-based dosing, unless otherwise indicated (Erstad 2020).

General anesthesia

General anesthesia:

Note: For dosing in obese patients, use adjusted body weight for initial weight-based dosing (Schumann 2020). Individualize dosing based on patient factors and concomitant anesthetic agents.

Induction of anesthesia: Note: In high-risk patients (eg, debilitated, American Society of Anesthesiologists - Physical Status [ASA-PS] 3 or 4, hemodynamically compromised), avoid rapid bolus administration to minimize hypotension. Induction doses may be administered in divided doses.

Healthy adults, ASA-PS 1 or 2: IV: Usual total dose: 1 to 2.5 mg/kg.

Hemodynamic compromise or hypovolemia: IV: Usual total dose: 0.5 to 1.5 mg/kg.

Debilitated or ASA-PS 3 or 4: IV: Usual total dose: 0.5 to 1.5 mg/kg.

Maintenance of anesthesia:

Healthy adults, ASA-PS 1 or 2:

Continuous IV infusion: Usual dosing range: 50 to 200 mcg/kg/minute; titrate to clinical response.

Debilitated or ASA-PS 3 or 4:

Continuous IV infusion: Usual dosing range: 50 to 100 mcg/kg/minute; titrate to clinical response.

Rapid sequence intubation outside the operating room

Rapid sequence intubation outside the operating room (induction): Note: May cause dose-related hypotension; consider alternative agent in patients who are hemodynamically unstable. Refer to local/state regulations and institutional policies and procedures regarding administration and monitoring requirements.

IV: 1.5 to 2 mg/kg once; usual dose range: 1 to 3 mg/kg. Note: Continuous infusion may be started if longer sedation is required (see "Mechanically Ventilated Patients in the ICU, Sedation") (Caro 2020; Roberts 2019; Stollings 2014).

Sedation

Sedation:

Mechanically ventilated patients in the ICU, sedation: Note: Used as part of a multimodal strategy (eg, combination of sedatives and analgesics) for ICU sedation and preferred over a benzodiazepine due to less risk of prolonged sedation and improved time to extubation; titrate to maintain a light level of sedation (eg, Richmond Agitation Sedation Scale 0 to −2) or clinical effect (eg, ventilator synchrony) (SCCM [Devlin 2018]).

Continuous IV infusion: Initial: 5 mcg/kg/minute; increase by 5 to 10 mcg/kg/minute every 5 to 10 minutes until goal sedation level is achieved. Usual maintenance dose: 5 to 50 mcg/kg/minute. Maximum dose (not well defined; may vary by institution): 60 to 80 mcg/kg/minute. Daily awakening trials or use of nurse-protocolized sedation are recommended; generally, titrate down slowly to avoid rapid awakening. If agitated after discontinuation of continuous infusion, then restart at ~50% of the previous maintenance dose (Jakob 2012; Kress 2000; Roberts 2009; SCCM [Barr 2013]; SCCM [Devlin 2018]).

Monitored anesthesia care: Note: For dosing in obese patients, use adjusted body weight for initial weight-based dosing (Schumann 2020). Doses should be individualized based on patient factors and concomitant sedatives and analgesics.

Healthy adults, ASA-PS 1 or 2:

Continuous IV infusion: Initial: 25 to 75 mcg/kg/minute; titrate to adequate sedation. Note: If rapid effect is desired, may initiate with a higher infusion rate (eg, 100 to 150 mcg/kg/minute for 3 to 5 minutes) or administer an initial bolus (eg, 0.25 to 0.5 mg/kg) (Rosero 2020; manufacturer's labeling).

or

IV: Intermittent bolus: 10 to 20 mg; may give additional doses as needed to achieve adequate sedation (Rosero 2020; manufacturer labeling).

Debilitated or ASA-PS 3 or 4: Use reduced dose. Bolus slowly and avoid rapid repeat dosing.

Procedural sedation, outside the operating room (off-label use): Note: Monitor respiratory and cardiovascular systems; refer to local/state regulations and institutional policies and procedures regarding administration and monitoring requirements.

IV: Initial: 0.5 to 1 mg/kg, followed by 0.25 to 0.5 mg/kg every 1 to 3 minutes, as needed, to achieve adequate sedation (ACEP [Miller 2019]; Roberts 2019). Some experts use a combination of propofol and ketamine (0.5 to 0.75 mg/kg dose for each drug) (ACEP [Godwin 2014]).

Status epilepticus, refractory

Status epilepticus, refractory (off-label use):

Note: Used as an alternative or adjunctive agent to midazolam, barbiturates, or ketamine after conventional intermittent therapies have failed. Mechanical ventilation and hemodynamic support required; continuous EEG is recommended. Titrate doses to cessation of electrographic seizures or burst suppression (Legriel 2017; NCS [Brophy 2012]; Rai 2018). Optimal regimen and dose are uncertain; refer to institutional protocol.

IV: Loading dose: 1 to 2 mg/kg, followed by 0.5 to 2 mg/kg every 3 to 5 minutes until seizures are suppressed; maximum total dose: 10 mg/kg (Legriel 2017; NCS [Brophy 2012]; Rai 2018).

Continuous IV infusion: After initial loading dose, begin continuous infusion at an initial rate of 20 mcg/kg/minute; titrate to cessation of electrographic seizures or burst suppression. Usual dose range: 30 to 60 mcg/kg/minute. Maximum dose (not well defined and may vary by institution): 200 mcg/kg/minute. Use caution with doses >80 mcg/kg/minute for >48 hours (Legriel 2017; NCS [Brophy 2012]; Rai 2018).

For breakthrough status epilepticus, administer bolus of 0.5 to 2 mg/kg every 3 to 5 minutes in addition to increasing continuous infusion rate by 5 to 10 mcg/kg/minute every 5 minutes (Legriel 2017; NCS [Brophy 2012]; Rai 2018).

Note: Generally, a period of at least 24 hours of electrographic suppression is suggested prior to down titrating the continuous infusion; withdraw gradually by decreasing the dose 15% to 20% every 3 hours while continuing conventional therapies (Drislane 2020; Legriel 2017; NCS [Brophy 2012]).

Dosing: Kidney Impairment: Adult

No dosage adjustment necessary.

Dosing: Hepatic Impairment: Adult

No dosage adjustment necessary.

Dosing: Pediatric

(For additional information see "Propofol: Pediatric drug information")

Note: FDA has issued an emergency use authorization (EUA) during the COVID-19 pandemic to permit the emergency use of the unapproved products, Propofol-Lipuro 1% (propofol 10 mg/mL) and Fresenius Propoven 2% (propofol 20 mg/mL) emulsion for ICU sedation in mechanically-ventilated patients >16 years of age. Fresenius Propoven 2% (20 mg/mL) is composed of medium and long-chained triglycerides and is double the concentration of the FDA-approved propofol 1% (10 mg/mL) products (eg, Diprivan). There is a risk of unintentional overdose and extra caution should be used to ensure appropriate product selection. Health care providers should review the Fact Sheet for Health Care Providers for key differences between products:

Propofol-Lipuro 1% Fact Sheet: https://www.fda.gov/media/146681/download.

Propoven 2% Fact Sheet: https://www.fda.gov/media/137889/download.

Note: Consult local regulations and individual institutional policies and procedures; should only be used by experienced personnel who are not actively engaged in the procedure or surgery; if used in a nonintubated and/or nonmechanically ventilated patient, qualified personnel and appropriate equipment for rapid institution of respiratory and/or cardiovascular support must be immediately available.

Dosage must be individualized based on total body weight and titrated to the desired clinical effect; wait at least 3 to 5 minutes between dosage adjustments to clinically assess drug effects; smaller doses are required when used with opioids; the following are general dosing guidelines (see "Abbreviations, Acronyms, and Symbols" section in front section for explanation of ASA-PS classes).

Anesthesia, general: Note: Increase dose in patients with chronic alcoholism (Fassoulaki 1993); decrease dose with acutely intoxicated (alcoholic) patients.

Induction of general anesthesia: Children and Adolescents (healthy) 3 to 16 years, ASA-PS 1 or 2: IV: 2.5 to 3.5 mg/kg over 20 to 30 seconds; use a lower dose for ASA-PS 3 or 4.

Maintenance of general anesthesia: Infants ≥2 months, Children, and Adolescents (healthy), ASA-PS 1 or 2: IV infusion: General range: 125 to 300 mcg/kg/minute (7.5 to 18 mg/kg/hour); Initial dose immediately following induction: 200 to 300 mcg/kg/minute; then decrease dose after 30 minutes if clinical signs of light anesthesia are absent; usual infusion rate after initial 30 minutes: 125 to 150 mcg/kg/minute (7.5 to 9 mg/kg/hour); younger pediatric patients may need higher infusion rates than older pediatric patients.

Procedural sedation: Limited data available: Infants, Children, and Adolescents: IV:

Repeated bolus method: Usual initial dose: 1 mg/kg; reported range for initial dose: 1 to 2 mg/kg; follow initial dose with 0.5 mg/kg every 3 to 5 minutes as needed until adequate level of sedation achieved (ACEP [Godwin 2014]; Bedirli 2012; Cho 2010; Ince 2013; Krauss 2006).

IV bolus followed by continuous infusion: Initial bolus: 1 to 2 mg/kg; continuous infusion: Reported initial rate and titration are variable (Machata 2010; Srinivasan 2012; Vespasiano 2007). In a large report of a pediatric sedation program in >4,000 patients (age range: 1 month to 21 years), after an initial bolus of at least 2 mg/kg, an infusion was started at an initial rate of 9 mg/kg/hour (150 mcg/kg/minute) and titrated as required; supplemental doses of 1 to 2 mg/kg were used as needed; however, hypotension occurred in up to 42.5% of patients undergoing MRI and 23.2% of patients undergoing other procedures (Vespasiano 2007). In a smaller trial of 138 young pediatric patients (age range: 3 months to 6 years), after a 1 mg/kg bolus, an infusion was initiated at an initial rate of 5 mg/kg/hour (83 mcg/kg/minute) and then titrated upward in 1 mg/kg/hour increments (to a maximum of 8 mg/kg/hour [133 mcg/kg/minute]) with additional boluses of 0.5 mg/kg given as needed to achieve adequate sedation level (Machata 2010).

Propofol with concurrent ketamine; emergency department procedures: IV: 0.5 to 0.75 mg/kg (ACEP [Godwin 2014]).

Note: When utilized by an organized service with trained and credentialed personnel, propofol use for procedural sedation outside of the operating room was shown to have low risk for serious adverse outcomes (Cravero 2009; Kamat 2015).

Status epilepticus; refractory: Limited data available: Children and Adolescents: Note: Several experts have expressed concern when using propofol for this indication in infants and children due to the risk for propofol-related infusion syndrome, particularly when administered in conjunction with a ketogenic diet or when given at high doses for prolonged periods of time (Baumeister 2004; Iyer 2009). Neurocritical Care Society guidelines for status epilepticus state that use of propofol in young children is contraindicated (NCS [Brophy 2010]):

Initial propofol infusion: IV: Loading dose 1 to 2 mg/kg, then initiate continuous IV infusion at 1.2 mg/kg/hour (20 mcg/kg/minute); titrate to desired effect (eg, burst suppression on EEG); usual range: 1.8 to 12 mg/kg/hour (30 to 200 mcg/kg/minute) (NCS [Brophy 2012]). Note: Use caution when administering high doses (>4 mg/kg/hour [>65 mcg/kg/minute]) for extended periods of time (>48 hours); monitor closely for adverse effects (eg, PRIS) (NCS [Brophy 2012]).

Breakthrough seizure while on propofol infusion: IV: Increase infusion rate by 0.3 to 0.6 mg/kg/hour (5 to 10 mcg/kg/minute) every 5 minutes with or without an additional 1 mg/kg bolus (NCS [Brophy 2012]).

Dosing: Kidney Impairment: Pediatric

No dosage adjustment necessary.

Dosing: Hepatic Impairment: Pediatric

No dosage adjustment necessary.

Dosing: Older Adult

Refer to adult dosing. Prior to use, consult local/state regulations and institutional policies and procedures regarding administration and monitoring requirements. Dosage must be individualized and titrated to the desired clinical effect. Wait at least 3 to 5 minutes between dosage adjustments to clinically assess drug effects. Smaller doses are generally required in elderly patients and when used with opioids.

Dosing: Obesity: Adult

The recommendations for dosing in patients who are obese are based upon the best available evidence and clinical expertise. Senior Editorial Team: Jeffrey F. Barletta, PharmD, FCCM; Manjunath P. Pai, PharmD, FCP; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC.

Class 1, 2, or 3 obesity (BMI ≥30 kg/m2):

IV: Use adjusted body weight for initial weight-based dose calculations, then titrate to clinical effect (Erstad 2020; expert opinion). Clinicians should not change dosing weight from one weight metric to another during therapy (ie, adjusted body weight to/from actual body weight) (expert opinion). Refer to adult dosing for indication-specific doses.

Rationale for recommendations: Weight-based dosing calculations using actual body weight for bolus doses or continuous infusions may lead to excessive concentrations (Erstad 2020; McLeay 2009); therefore, use of an alternative size descriptor (eg, adjusted body weight) is recommended for dosing propofol in patients with obesity (expert opinion). The majority of studies evaluated pharmacokinetic and pharmacodynamics of propofol when used during induction and/or maintenance of anesthesia (Araújo 2018; Araújo 2019; McLeay 2009; Xu 2020). Even though lean body weight (LBW) appears to have the best correlation to volume of distribution and clearance, the use of the complex LBW formula is not recommended because of concerns with calculation errors, especially in critical situations, and concerns with underdosing in situations where rapid sedation is preferred (eg, induction of anesthesia) (Janmahasatian 2005; expert opinion).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Emulsion, Intravenous:

Diprivan: 100 mg/10 mL (10 mL); 200 mg/20 mL (20 mL); 500 mg/50 mL (50 mL); 1000 mg/100 mL (100 mL) [contains edetate (edta) disodium, egg phospholipids (egg lecithin), glycerin, soybean oil]

Fresenius Propoven: 2000 mg/100 mL (100 mL) [contains egg phosphatides, soybean oil]

Propofol-Lipuro: 1000 mg/100 mL (100 mL) [contains egg phosphatides, soybean oil]

Generic: 1000 mg/100 mL (100 mL); 200 mg/20 mL (20 mL); 500 mg/50 mL (50 mL)

Emulsion, Intravenous [preservative free]:

Diprivan: 200 mg/20 mL (20 mL) [contains edetate (edta) disodium, egg phospholipids (egg lecithin), soybean oil]

Fresenius Propoven: 200 mg/20 mL (20 mL); 500 mg/50 mL (50 mL); 1000 mg/100 mL (100 mL) [contains egg phosphatides, soybean oil]

Generic: 1000 mg/100 mL (100 mL); 200 mg/20 mL (20 mL); 500 mg/50 mL (50 mL)

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Emulsion, Intravenous:

Diprivan: 10 mg/mL (20 mL, 50 mL, 100 mL) [contains edetate (edta) disodium, egg phosphatides, soybean oil]

Generic: 10 mg/mL (20 mL, 50 mL, 100 mL)

Prescribing and Access Restrictions

The FDA has issued an emergency use authorization (EUA) during the COVID-19 pandemic to permit the emergency use of the unapproved products, Propofol-Lipuro 1% (propofol 10 mg/mL) emulsion and Fresenius Propoven 2% (propofol 20 mg/mL) emulsion. As part of the EUA, fact sheets pertaining to emergency use of these products are required to be available for health care providers and patients/caregivers and certain mandatory requirements for administration under the EUA must be met as outlined in the FDA EUA letter; the fact sheets and EUA letter may be accessed at:

Propofol-Lipuro 1%:

EUA Letter: https://www.fda.gov/media/146680/download

Fact Sheet for Health Care Providers: https://www.fda.gov/media/146681/download

Fact Sheet for Patients and Parent/Caregivers: https://www.fda.gov/media/146682/download

Propoven 2%:

EUA Letter: https://www.fda.gov/media/137888/download

Fact Sheet for Health Care Providers: https://www.fda.gov/media/137889/download

Fact Sheet for Patients And Parent/Caregivers: https://www.fda.gov/media/137890/download

Additionally, health care providers must track and report all medication errors and serious adverse events potentially associated with these products by either submitting a MedWatch form (https://www.fda.gov/medwatch/report.htm) or FDA Form 3500 (health professional) by fax (1-800-FDA-0178).

Administration: Adult

Note : FDA has issued an emergency use authorization (EUA) during the COVID-19 pandemic to permit the emergency use of the unapproved products, Propofol-Lipuro 1% (propofol 10 mg/mL) and Fresenius Propoven 2% (propofol 20 mg/mL) emulsion. Because Fresenius Propoven 2% contains double the concentration of propofol (20 mg/mL) compared to the FDA-approved propofol products (10 mg/mL), there is a risk of unintentional overdose. Propofol-Lipuro 1% and Fresenius Propoven 2% do not contain antimicrobial retardants; strict aseptic technique must be maintained during use. Health care providers should review the Fact Sheet for Health Care Providers for key differences between products:

Propofol-Lipuro 1% Fact Sheet: https://www.fda.gov/media/146681/download

Propoven 2% Fact Sheet: https://www.fda.gov/media/137889/download

IV: Administer intermittent bolus or by continuous IV infusion. Prior to use, consult local/state regulations and institutional policies and procedures regarding administration and monitoring requirements. Strict aseptic technique must be maintained in handling although a preservative has been added. Do not use if contamination is suspected. Do not administer through the same IV catheter with blood or plasma. Tubing and any unused portions of propofol vials should be discarded after 12 hours.

To reduce pain associated with injection, use larger veins of forearm or antecubital fossa; lidocaine IV (1 mL of a 1% solution) may also be used prior to administration or it may be added to propofol immediately before administration in a quantity not to exceed 20 mg lidocaine per 200 mg propofol. Do not use filter <5 micron for administration.

Administration: Pediatric

Note: FDA has issued an emergency use authorization (EUA) during the COVID-19 pandemic to permit the emergency use of the unapproved products, Propofol-Lipuro 1% (propofol 10 mg/mL) and Fresenius Propoven 2% (propofol 20 mg/mL) emulsion for ICU sedation in mechanically-ventilated patients >16 years of age. Fresenius Propoven 2% (20 mg/mL) is composed of medium and long-chained triglycerides and is double the concentration of the FDA-approved propofol 1% (10 mg/mL) products (eg, Diprivan). There is a risk of unintentional overdose and extra caution should be used to ensure appropriate product selection. Propofol-Lipuro 1% and Fresenius Propoven 2% do not contain antimicrobial retardants; strict aseptic technique must be maintained during use. Health care providers should review the Fact Sheet for Health Care Providers for key differences between products:

Propofol-Lipuro 1% Fact Sheet: https://www.fda.gov/media/146681/download.

Propoven 2% Fact Sheet: https://www.fda.gov/media/137889/download.

Note: Consult local regulations and individual institutional policies and procedures.

Parenteral: IV: FDA approved products: Propofol 1% (10 mg/mL) (eg, Diprivan): Strict aseptic technique must be maintained in handling. Shake emulsion well before use. May be administered undiluted or may be further diluted with D5W. Do not administer via filter with <5-micron pore size. Do not administer through the same IV catheter with blood or plasma. Tubing and any unused portions of propofol vials should be discarded after 12 hours.

To reduce pain associated with injection, use larger veins of forearm or antecubital fossa; lidocaine IV (1 mL of a 1% solution) may also be used prior to administration or lidocaine may be added to propofol immediately before administration.

Induction: Administer pediatric induction doses over 20 to 30 seconds

Maintenance: Administer at a concentration of 2 to 10 mg/mL at prescribed rate

Use: Labeled Indications

General anesthesia: Induction of anesthesia in patients ≥3 years of age; maintenance of anesthesia in patients ≥2 months of age.

Mechanically ventilated patients in the ICU, sedation: Sedation of intubated, mechanically ventilated adults in the ICU.

Monitored anesthesia care sedation: Initiation and maintenance of monitored anesthesia care sedation in adults.

Sedation and regional anesthesia: Combined sedation and regional anesthesia in adults.

Note: Consult local regulations and individual institutional policies and procedures.

Use: Off-Label: Adult

Procedural sedation, outside the operating room; Status epilepticus, refractory

Medication Safety Issues
Sound-alike/look-alike issues:

Diprivan may be confused with Diflucan, Ditropan

Propofol may be confused with fospropofol

Propofol may be confused with bupivacaine (liposomal) due to similar white, milky appearance.

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.

Pediatric patients: High-risk medication:

KIDs List: Propofol is identified on the Key Potentially Inappropriate Drugs in Pediatrics (KIDs) list; use should be avoided at doses >4 mg/kg/hour for >48 hours due to risk of propofol-related infusion syndrome; the incidence is higher in children and adolescents than adults because of higher relative doses of propofol required, especially in status epilepticus (strong recommendation; moderate quality of evidence) (PPA [Meyers 2020]).

Administration issues:

Propofol may be confused with bupivacaine liposome injectable suspension (Exparel) in operating rooms and other surgical areas due to their similar white, milky appearance especially when prepared in syringes. Bupivacaine liposome injectable suspension (Exparel) is intended only for administration via infiltration into the surgical site (and not for systemic use). Confusion with propofol may lead to accidental intravenous administration of Exparel instead of the intended propofol. Therefore, to avoid potential confusion ISMP recommends that all vials be separated when stocked in common areas and all prepared syringes be labeled.

Adverse Reactions (Significant): Considerations
Cardiac conduction disturbances

Propofol may cause bradyarrhythmias (bradycardia) and convert tachyarrhythmias (tachycardia) to sinus rhythm (Ref). May also be associated rarely with prolonged QT interval on ECG (Ref) and ECG abnormality (shortening of the QT interval) (Ref).

Mechanism: Not clearly established; may be direct or indirect (more emerging data). Indirect effect may be related to modulation of autonomic nervous system tone through changes in the baroreceptor reflex, resulting in bradycardia (Ref). QT prolongation is most likely relegated to dose and predisposed cardiac conditions (Ref).

Onset: Rapid; both bradycardia and QT prolongation have been reported to occur rapidly (Ref).

Risk factors:

Bradycardia (possible risk factors):

• High doses, prolonged duration of therapy (in association with propofol-related infusion syndrome [PRIS]) (Ref)

• Concurrent medications, such as beta-blockers, neostigmine, neuromuscular blockers, opioids (Ref)

• Previous cardiac history (Ref)

• Surgical issues, such as extradural anesthesia, previous syncope, preoperative conduction abnormalities, too light anesthesia (Ref)

QT prolongation:

• Drug-specific:

- High doses (Ref)

- Pediatric patients (in association with PRIS) (Ref)

• General:

- Females (Ref)

- Age >65 years (Ref)

- Structural heart disease (eg, history of myocardial infarction or heart failure with reduced ejection fraction) (Ref)

- Genetic defects of cardiac ion channels (Ref)

- History of drug-induced torsades de pointes (Ref)

- Congenital long QT syndrome (Ref)

- Baseline QTc interval prolongation (eg, >500 msec) or lengthening of the QTc by ≥60 msec (Ref)

- Electrolyte disturbances (eg, hypocalcemia, hypokalemia, hypomagnesemia) (Ref)

- Bradycardia (Ref)

- Hepatic impairment (Ref)

- Kidney impairment (Ref)

- Loop diuretic use (Ref)

- Sepsis (Ref)

- Concurrent administration of multiple medications (≥2) that prolong the QT interval or medications with drug interactions that increase serum concentrations of QT-prolonging medications (Ref)

Hypersensitivity reactions (immediate)

Propofol may rarely cause anaphylaxis (Ref), angioedema, and bronchoconstriction (Ref). Current evidence suggests that immediate hypersensitivity reactions associated with propofol are rare compared to other medications often administered at the same time (eg, antibiotics, neuromuscular blocking agents).

Mechanism: Non–dose-related; immunologic or nonimmunologic. Immediate hypersensitivity reactions (eg, anaphylaxis, urticaria) can be IgE-mediated or non–IgE-mediated (Ref). Propofol allergy may be due to the presence of the diisopropyl side chain or phenol group (Ref).

Onset: Immediate hypersensitivity reactions: rapid; occur shortly after administration (often within 5 to 10 minutes) (Ref); reported to occur after first exposure (Ref) or after multiple exposures to propofol (Ref).

Risk factors:

• Food allergy: Although propofol is mixed in a formulation containing soybean oil and egg lecithin, true allergy has been associated with soy and egg proteins and not these oils. Current evidence suggests that immediate hypersensitivity reactions associated with propofol are not predicted by a history of food allergy, including those with soy, egg, and peanut allergy (Ref). Available studies have indicated that propofol may be used safely in soy- or egg-allergic patients (Ref). A statement issued by the American Academy of Allergy, Asthma and Immunology has concluded that patients with soy or egg allergy can receive propofol without any special precautions (Ref).

Hypertriglyceridemia

Hypertriglyceridemia can occur with propofol, which may lead to acute pancreatitis. Rare cases of propofol-induced acute pancreatitis have occurred in the absence of hypertriglyceridemia (Ref).

Mechanism: Dose-and duration-related; propofol is formulated as a ~10% lipid emulsion, which can cause hypertriglyceridemia and lead to acute pancreatitis (Ref). Cases of propofol-induced acute pancreatitis that occur in the absence of hypertriglyceridemia have been described as idiosyncratic (Ref).

Onset: Rapid; hypertriglyceridemia may occur at any time during therapy, but the median time ranges from 2 to 4 days (Ref).

Risk factors:

Hypertriglyceridemia:

• Dose and duration: >50 mcg/kg/minute for >2 days (Ref)

• Higher severity of illness (Ref)

• Longer ICU stay (Ref)

• SARS-CoV-2 positive (Ref)

• Younger patients (Ref)

Acute pancreatitis:

• Preexisting diseases or factors that predispose to acute pancreatitis (eg, alcohol use disorder, abdominal or cardiothoracic surgeries, hypertriglyceridemia, diabetes, family history of lipoproteinemia, obesity) (Ref)

Hypotension

Propofol may cause severe hypotension (to the effect of ≥30% decrease in mean arterial pressure [MAP]), especially with bolus dosing or in the setting of hypovolemia, sepsis, or shock (Ref). May also induce hypotension in pediatric patients (neonates) and trauma patients (adults and pediatrics) (Ref). Propofol in neonatal endotracheal intubations may potentiate hypotension, leading to serious complications, such as intraventricular hemorrhage or periventricular leukomalacia (Ref).

Mechanism: Not clearly established; proposed mechanisms include reduction of peripheral resistance through a direct action in vascular smooth muscle (possibly from histamine release), inhibition of sympathetic activity on the vasculature (Ref), and reduction in stressed volume caused by decreased venous and arterial resistance with no change in cardiac output (Ref). Propofol acts as a calcium channel blocker and beta-adrenergic antagonist (Ref).

Onset: Rapid; propofol may induce hypotension after bolus administration, new continuous infusion initiation, or increases in the dose.

Risk factors:

• Bolus dosing

• Hypovolemia

• Older, debilitated, or American Society of Anesthesiologists - Physical Status (ASA-P) 3 or 4 patients

• Baseline MAP 60 to 70 mm Hg prior to propofol administration (Ref)

• Changes to propofol infusion rate (Ref)

• Need for renal replacement therapy during treatment with propofol (Ref)

• Rapid sequence intubation in patients (adults and pediatrics) with trauma (Ref)

• Sepsis (adults) (Ref)

• Severe aortic stenosis (Ref)

• Trauma patients (adults): Age >55 years, lower baseline systolic blood pressure, obesity (Ref)

• Preterm infants 29 to 32 gestational weeks with infant respiratory distress syndrome (Ref)

Propofol-related infusion syndrome (PRIS)

Propofol-related infusion syndrome (PRIS), is a serious adverse reaction that has been reported in adult and pediatric patients (Ref). PRIS is rare but has a high mortality rate and is characterized by a constellation of symptoms, including dysrhythmia (bradycardia or tachycardia), widening of the QRS complex, heart failure, hypotension, asystole, lipemia and hypertriglyceridemia, metabolic acidosis, and/or rhabdomyolysis or myoglobinuria with acute kidney injury and hyperkalemia (Ref).

Mechanism: Dose- and duration-related; may be due to a mitochondrial defect (Ref). It is thought that propofol inhibits transportation of long-chain fatty acids into the cell and interferes with/uncouples oxidative phosphorylation (Ref).

Onset: Rapid; between 1 to 4 days (Ref).

Risk factors:

• Dose and duration: Usually ≥4 mg/kg/hour for ≥2 days (Ref), but has also been reported following large dose, short-term infusions during surgical anesthesia. PRIS has also been reported with lower-dose infusions (Ref)

• Young age (Ref)

• Catecholamine, corticosteroid, or vasopressor use (Ref)

• Critical illness (Ref)

• High fat, low carbohydrate intake (Ref)

• Inborn error of fatty acid oxidation (Ref)

• Males (Ref)

• Decreased oxygen delivery to tissues

• Sepsis

• Serious neurological injury

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Cardiovascular: Hypotension (3% to 26%)

Local: Burning sensation at injection site (≤18%), pain at injection site (includes stinging; ≤18%)

Nervous system: Involuntary body movements (3% to 17%)

Respiratory: Apnea (30 to 60 seconds duration: 10% to 24% ; >60 seconds duration: 5% to 12%)

1% to 10%:

Cardiovascular: Bradycardia (1% to 3%), cardiac arrhythmia (1% to 3%), hypertension (1% to 8%), low cardiac output (1% to 3%; concurrent opioid use increases incidence), tachycardia (1% to 3%)

Dermatologic: Pruritus (1% to 3%), skin rash (1% to 5%)

Endocrine & metabolic: Hypertriglyceridemia (3% to 10%), respiratory acidosis (during weaning; 3% to 10%)

<1%:

Cardiovascular: Asystole, atrial arrhythmia, atrial premature contractions, bigeminy, flushing, phlebitis, syncope, thrombosis, ventricular premature contractions

Endocrine & metabolic: Hypomagnesemia

Gastrointestinal: Nausea, pancreatitis (Asghar 2020), sialorrhea

Genitourinary: Cloudy urine, urine discoloration (green)

Hematologic & oncologic: Hemorrhage, leukocytosis

Hypersensitivity: Anaphylaxis (Koul 2011), nonimmune anaphylaxis (McHale 1992)

Nervous system: Agitation, anticholinergic syndrome, chills, delirium, dizziness, drowsiness, dystonia, hypertonia, loss of consciousness (postoperative; with or without increased muscle tone), myoclonus (including perioperative; rarely including seizure and opisthotonos) (Tam 2009), paresthesia

Neuromuscular & skeletal: Laryngospasm, limb pain, myalgia, rhabdomyolysis (Zarovnaya 2007)

Ophthalmic: Amblyopia, visual disturbance

Respiratory: Cough, decreased lung function, hypoxia (Hanna 1998), pulmonary edema (Waheed 2014), wheezing

Miscellaneous: Fever

Frequency not defined: Respiratory: Dyspnea, hypoventilation, upper airway obstruction

Postmarketing:

Cardiovascular: ECG abnormality (shortening of the QT interval) (Erdil 2009), prolonged QT interval on ECG (Kim 2008)

Endocrine & metabolic: Metabolic acidosis (Chukwuemeka 2006)

Hypersensitivity: Angioedema (You 2012)

Respiratory: Bronchoconstriction (Nishiyama 2001)

Miscellaneous: Infusion related reaction (propofol-related infusion syndrome) (Krajčová 2015)

Contraindications

Hypersensitivity to propofol or any component of the formulation; hypersensitivity to eggs, egg products, soybeans, or soy products; when general anesthesia or sedation is contraindicated.

Note: Although the manufacturer's labeling lists egg allergy as a contraindication, available studies (mostly retrospective) and an American Academy of Allergy, Asthma, and Immunology statement have suggested that propofol may be used safely in soy- or egg-allergic patients (AAAAI [Lieberman 2015]; AAAAI 2019; Asserhøj 2016; Dziedzic 2016; Murphy 2011). In patients with more severe soy or egg allergy, some experts recommend the use of an alternative anesthetic or a small trial dose of propofol prior to full dose administration (Sicherer 2020).

Canadian labeling: Additional contraindication (not in US labeling): Hypersensitivity to lipid emulsions; sedation of children ≤18 years of age receiving intensive care.

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylaxis/hypersensitivity reactions: May rarely cause hypersensitivity, anaphylaxis, anaphylactoid reactions, angioedema, bronchospasm, and erythema; medications for the treatment of hypersensitivity reactions should be available for immediate use. Use with caution in patients with history of hypersensitivity/anaphylactic reaction to peanuts; a low risk of cross-reactivity between soy and peanuts may exist. According to the manufacturer, use is contraindicated in patients who are hypersensitive to eggs, egg products, soybeans, or soy products. However, available studies (mostly retrospective) and an American Academy of Allergy, Asthma, and Immunology statement have suggested that propofol may be used safely in soy- or egg-allergic patients (AAAAI [Lieberman 2015]; AAAAI 2019; Asserhøj 2016; Dziedzic 2016; Murphy 2011). In patients with more severe soy or egg allergy, some experts recommend the use of an alternative anesthetic or a small trial dose of propofol prior to full dose administration (Sicherer 2020).

• ECG effects: In most cases, propofol does not significantly affect the QT interval (Staikou 2014). However, prolongation of the QT interval, usually within normal limits, has occurred in case reports and small prospective studies and may be dose dependent (Hume-Smith 2008; Kim 2008; McConachie 1989; Saarnivaara 1990; Saarnivaara 1993; Sakabe 2002). Shortening of the QT interval has also occurred (Erdil 2009; Tanskanen 2002).

• Hypertriglyceridemia: Because propofol is formulated within a 10% fat emulsion, hypertriglyceridemia is an expected side effect. Patients who develop hypertriglyceridemia (eg, ≥400 mg/dL) are at risk of developing pancreatitis. Serum triglyceride levels should be obtained prior to initiation of therapy and every 3 to 7 days thereafter. Monitor serum triglycerides when infusions last >48 hours or infusion rates are >50 mcg/kg/minute (Devlin 2005). An alternative sedative agent should be employed if significant hypertriglyceridemia occurs. Use with caution in patients with preexisting hyperlipidemia as evidenced by increased serum triglyceride levels or serum turbidity.

• Hypotension: The major cardiovascular effect of propofol is hypotension especially if patient is hypovolemic or if bolus dosing is used. Hypotension may be substantial with a reduction in mean arterial pressure occasionally exceeding 30%. Use with caution in patients who are hemodynamically unstable, hypovolemic, or have abnormally low vascular tone (eg, sepsis).

• Injection-site reaction: Transient local pain may occur during IV injection; lidocaine 1% solution may be administered prior to administration or may be added to propofol immediately prior to administration to reduce pain associated with injection (see Administration).

• Myoclonus: Perioperative myoclonus (eg, convulsions and opisthotonos) has occurred with administration.

• Propofol-related infusion syndrome: Propofol-related infusion syndrome (PRIS) is a serious side effect with a high mortality rate (up to 33%) characterized by dysrhythmia (eg, bradycardia or tachycardia), heart failure, hyperkalemia, lipemia, metabolic acidosis, and/or rhabdomyolysis or myoglobinuria with subsequent renal failure. Risk factors include poor oxygen delivery, sepsis, serious cerebral injury, and the administration of high doses of propofol (usually doses >83 mcg/kg/minute or >5 mg/kg/hour for >48 hours), but has also been reported following large dose, short-term infusions during surgical anesthesia. PRIS has also been reported with lower-dose infusions (Hemphill 2019; Krajčová 2015; Roberts 2009). The onset of the syndrome is rapid, occurring within 4 days of initiation. The mechanism of the syndrome has yet to be determined. Alternate sedative therapy should be considered for patients with escalating doses of vasopressors or inotropes, when cardiac failure occurs during high-dose propofol infusion, when metabolic acidosis is observed, or in whom lengthy and/or high-dose sedation is needed (Corbett 2008; SCCM [Barr 2013]).

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with severe cardiac disease (ejection fraction <50%) or hypotension; may have more profound adverse cardiovascular responses to propofol. In a scientific statement from the American Heart Association, propofol has been determined to be an agent that may exacerbate underlying myocardial dysfunction (magnitude: moderate) (AHA [Page 2016]).

• Increased intracranial pressure: Use with caution in patients with increased intracranial pressure or impaired cerebral circulation; substantial decreases in mean arterial pressure and subsequent decreases in cerebral perfusion pressure may occur; consider continuous infusion or administer as a slow bolus.

• Infection risk: Propofol vials and prefilled syringes have the potential to support the growth of various microorganisms despite product additives intended to suppress microbial growth. To limit the potential for contamination, strictly adhere to recommendations in product labeling for handling and administering propofol.

• Pancreatitis: Use with caution in patients with preexisting pancreatitis; use of propofol may exacerbate this condition.

• Respiratory disease: Use with caution in patients with respiratory disease.

• Seizure disorder: Use with caution in patients with a history of epilepsy or seizures; seizure may occur during recovery phase.

Concurrent drug therapy issues:

• Opioids: Concomitant use may lead to increased sedative or anesthetic effects of propofol, more pronounced decreases in systolic, diastolic, and mean arterial pressures and cardiac output; lower doses of propofol may be needed. In addition, fentanyl may cause serious bradycardia when used with propofol in pediatric patients. Alfentanil use with propofol has precipitated seizure activity in patients without any history of epilepsy.

Special populations:

• American Society of Anesthesiologists - Physical Status (ASA-PS) 3 or 4 patients: Use a lower induction dose, a slower maintenance rate of administration, and avoid rapidly delivered boluses in ASA-PS 3 or 4 patients to reduce the incidence of unwanted cardiorespiratory depressive events.

• Debilitated patients: Use a lower induction dose, a slower maintenance rate of administration, and avoid rapidly delivered boluses in debilitated patients to reduce the incidence of unwanted cardiorespiratory depressive events.

• Elderly: Use a lower induction dose, a slower maintenance rate of administration, and avoid rapidly delivered boluses in elderly patients to reduce the incidence of unwanted cardiorespiratory depressive events.

• Pediatric neurotoxicity: In pediatric and neonatal patients <3 years of age and patients in third trimester of pregnancy (ie, times of rapid brain growth and synaptogenesis), the repeated or lengthy exposure to sedatives or anesthetics during surgery/procedures may have detrimental effects on child or fetal brain development and may contribute to various cognitive and behavioral problems. Epidemiological studies in humans have reported various cognitive and behavioral problems including neurodevelopmental delay (and related diagnoses), learning disabilities, and ADHD. Human clinical data suggest that single, relatively short exposures are not likely to have similar negative effects. No specific anesthetic/sedative has been found to be safer. For elective procedures, risk vs benefits should be evaluated and discussed with parents/caregivers/patients; critical surgeries should not be delayed (FDA 2016).

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer's labeling.

• Edetate disodium: Some formulations contain edetate disodium which may lead to decreased zinc levels in patients with prolonged therapy (>5 days) or a predisposition to zinc deficiency (eg, burns, diarrhea, or sepsis). A holiday from propofol infusion should take place after 5 days of therapy to allow for evaluation and necessary replacement of zinc.

• Sulfites: Some formulations may contain sulfites.

Other warnings/precautions:

• Abrupt discontinuation: Avoid abrupt discontinuation prior to weaning or daily wake up assessments. Abrupt discontinuation can result in rapid awakening, anxiety, agitation, and resistance to mechanical ventilation; wean the infusion rate so the patient awakens slowly. Discontinue opioids and paralytic agents prior to weaning. Long-term infusions can result in some tolerance; taper propofol infusions to prevent withdrawal.

• Analgesic supplementation: Propofol lacks analgesic properties; pain management requires specific use of analgesic agents, at effective dosages, propofol must be titrated separately from the analgesic agent.

• Experienced personnel: Use requires careful patient monitoring, should only be used by experienced personnel who are not actively engaged in the procedure or surgery. If used in a nonintubated and/or nonmechanically ventilated patient, qualified personnel and appropriate equipment for rapid institution of respiratory and/or cardiovascular support must be immediately available. Use to induce moderate (conscious) sedation in patients warrants monitoring equivalent to that seen with deep anesthesia. Consult local regulations and individual institutional policies and procedures.

Warnings: Additional Pediatric Considerations

In pediatric and neonatal patients <3 years of age and patients in third trimester of pregnancy (ie, times of rapid brain growth and synaptogenesis), the repeated or lengthy exposure to sedatives or anesthetics during surgery/procedures may have detrimental effects on the child’s or fetus’ brain development and may contribute to various cognitive and behavioral problems; the FDA is requiring warnings be included in the manufacturer’s labeling for all general anesthetic/sedative drugs. Multiple animal species studies have shown adverse effects on brain maturation; in juvenile animals, drugs that potentiate GABA activity and/or block NMDA receptors for >3 hours demonstrated widespread neuronal and oligodendrocyte cell loss along with alteration in synaptic morphology and neurogenesis. Epidemiological studies in humans have reported various cognitive and behavioral problems including neurodevelopmental delay (and related diagnoses), learning disabilities, and ADHD. Human clinical data suggest that single, relatively short exposures are not likely to have similar negative effects. Further studies are needed to fully characterize findings and ensure that these findings are not related to underlying conditions or the procedure itself. No specific anesthetic/sedative has been found to be safer. For elective procedures, risk vs benefits should be evaluated and discussed with parents/caregivers/patients; critical surgeries should not be delayed (FDA 2016).

Use extreme caution when using for refractory status epilepticus because higher doses are often required to control seizures for an extended period of time (in pediatric patients: doses >65 mcg/kg/minute (4 mg/kg/hour) for >48 hours) which may increase risk for propofol-related infusion syndrome (NCS [Brophy 2012]). Fatal cardiac failure has also been reported with concurrent ketogenic diet and propofol therapy (Baumeister 2004).

Propofol use for procedural sedation outside of the operating room was shown to have low risk for serious adverse outcomes when utilized by an organized service with trained and credentialed personnel. Data was collected by the Pediatric Sedation Research Consortium from 37 institutions including 49,836 encounters. There were no deaths, two cardiopulmonary resuscitations, and four aspiration events (Cravero 2009). The same study group reported an additional 5 years of data with an additional 91,189 encounters and showed similar findings. In comparison to the earlier time period, the incidence of airway obstruction was lower (1.6%). Risk factors for adverse reaction included: primary diagnosis of respiratory infection, prematurity, concomitant medications, and certain procedure locations (eg, dental clinic, catheter lab) (Kamat 2015).

Metabolism/Transport Effects

Substrate of CYP1A2 (minor), CYP2A6 (minor), CYP2B6 (minor), CYP2C19 (minor), CYP2C9 (minor), CYP2D6 (minor), CYP2E1 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP3A4 (weak)

Drug Interactions

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy

Alfentanil: May enhance the adverse/toxic effect of Propofol. Specifically the development of opisthotonus (severe hyperextension and spasticity resulting in arching or bridging position) and/or tonic clonic seizures. Risk C: Monitor therapy

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

ALPRAZolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ALPRAZolam. Risk C: Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification

Amisulpride (Oral): May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy

Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Risk C: Monitor therapy

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification

Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

Cannabis: May diminish the therapeutic effect of Propofol. Risk C: Monitor therapy

CarBAMazepine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy

Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Risk D: Consider therapy modification

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy

Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Risk C: Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Risk C: Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy

EPHEDrine (Systemic): Propofol may enhance the therapeutic effect of EPHEDrine (Systemic). Risk C: Monitor therapy

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

FentaNYL: Propofol may enhance the CNS depressant effect of FentaNYL. Management: Consider alternatives to this combination when possible. If the combination is used, monitor more closely for bradycardia, apnea, and excessive CNS depression. Propofol induction dose requirements may be reduced. Pediatric patients may be at greater risk. Risk D: Consider therapy modification

Fexinidazole: Bradycardia-Causing Agents may enhance the arrhythmogenic effect of Fexinidazole. Risk X: Avoid combination

Finerenone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Finerenone. Risk C: Monitor therapy

Fingolimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Fingolimod. Management: Consult with the prescriber of any bradycardia-causing agent to see if the agent could be switched to an agent that does not cause bradycardia prior to initiating fingolimod. If combined, perform continuous ECG monitoring after the first fingolimod dose. Risk D: Consider therapy modification

Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Risk C: Monitor therapy

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy

Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Risk C: Monitor therapy

Ixabepilone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ixabepilone. Risk C: Monitor therapy

Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Risk C: Monitor therapy

Lemborexant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Risk D: Consider therapy modification

Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification

Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy

Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Risk D: Consider therapy modification

Lonafarnib: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lonafarnib. Management: Avoid concurrent use of lonafarnib with weak CYP3A4 inhibitors. If concurrent use is unavoidable, reduce the lonafarnib dose to or continue at a dose of 115 mg/square meter. Monitor for evidence of arrhythmia, syncope, palpitations, or similar effects. Risk D: Consider therapy modification

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Melatonin: May enhance the therapeutic effect of Propofol. Risk C: Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification

Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy

Midazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Midazolam. Risk C: Monitor therapy

Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Risk C: Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification

Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Ozanimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Risk X: Avoid combination

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy

Ponesimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Ponesimod. Management: Avoid coadministration of ponesimod with drugs that may cause bradycardia when possible. If combined, monitor heart rate closely and consider obtaining a cardiology consult. Do not initiate ponesimod in patients on beta-blockers if HR is less than 55 bpm. Risk D: Consider therapy modification

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

RifAMPin: May enhance the hypotensive effect of Propofol. Management: Avoid this combination if possible. Use of propofol in a patient who has been taking rifampin may result in clinically significant hypotension. Risk D: Consider therapy modification

Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy

Ropivacaine: Propofol may increase the serum concentration of Ropivacaine. Risk C: Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy

Simvastatin: CYP3A4 Inhibitors (Weak) may increase serum concentrations of the active metabolite(s) of Simvastatin. CYP3A4 Inhibitors (Weak) may increase the serum concentration of Simvastatin. Risk C: Monitor therapy

Siponimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. If combined, consider obtaining a cardiology consult regarding patient monitoring. Risk D: Consider therapy modification

Sirolimus (Conventional): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Conventional). Risk C: Monitor therapy

Sirolimus (Protein Bound): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Protein Bound). Management: Reduce the dose of protein bound sirolimus to 56 mg/m2 when used concomitantly with a weak CYP3A4 inhibitor. Risk D: Consider therapy modification

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

Tacrolimus (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy

Terlipressin: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination

Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Risk C: Monitor therapy

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (given at least 2 hours later if needed) of ubrogepant should be limited to 50 mg. Risk D: Consider therapy modification

Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Valproate Products: May enhance the therapeutic effect of Propofol. Risk C: Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification

Food Interactions

Edetate disodium, an ingredient of propofol emulsion, may lead to decreased zinc levels in patients on prolonged therapy (>5 days) or those predisposed to deficiency (burns, diarrhea, and/or major sepsis). Management: Zinc replacement therapy may be needed.

Pregnancy Considerations

Propofol crosses the placenta and may be associated with neonatal CNS and respiratory depression.

Based on animal data, repeated or prolonged use of general anesthetic and sedation medications that block N-methyl-D-aspartate (NMDA) receptors and/or potentiate gamma-aminobutyric acid (GABA) activity may affect brain development. Evaluate benefits and potential risks of fetal exposure to propofol when duration of surgery is expected to be >3 hours (Olutoye 2018).

Propofol is not recommended by the manufacturer for obstetrical use, including cesarean section deliveries. However, in cases where general anesthesia is needed for cesarean delivery, propofol has been used as an induction agent (ACOG 209 2019; Devroe 2015).

The ACOG recommends that pregnant patients should not be denied medically necessary surgery, regardless of trimester. If the procedure is elective, it should be delayed until after delivery (ACOG 775 2019).

Note: Propofol-Lipuro 1% (propofol 10 mg/mL) emulsion and Fresenius Propoven 2% (propofol 20 mg/mL) emulsion have been approved for emergency use during the COVID-19 pandemic. Both products contain medium chain triglycerides (MCT) and long chain triglycerides (LCT); prolonged exposure to MCT is associated with neural tube defects in animals. In addition, the Fresenius Propoven 2% formulation is double the concentration of FDA-approved products. Neither formulation approved under emergency use should be used in pregnant patients unless no other FDA-approved products are available to maintain sedation in patients who require mechanical ventilation in an ICU setting.

Breastfeeding Considerations

Propofol is present in breast milk.

In studies where propofol is used prior to cesarean delivery, exposure to the infant is low due to low concentrations in breast milk and low volume of breast milk produced within 24 hours' postpartum. When measurable, concentrations decrease quickly over time (Dailland 1989). Studies conducted in nine lactating women undergoing general surgery where propofol was used to induce anesthesia report propofol milk concentrations that are <1% of the total maternal dose. Except in one case where age was not clearly specified, infants in these studies were between 6 weeks and 15 months of age (Nitsun 2006; Stuttmann 2010).

A green discoloration to the breast milk was noted in a woman following administration of propofol during surgery for removal of an ectopic pregnancy. Although other medications were also administered, propofol was detected in the milk and assumed to be the cause; resolution of this effect occurred within 48 hours after surgery (Birkholz 2009). Dizziness or drowsiness were not observed in four breastfed infants. One was a 3-month old infant fed as early as ~90 minutes after maternal surgery (Stuttmann 2010).

Breastfeeding is not recommended by the manufacturer. The Academy of Breast Feeding Medicine recommends postponing elective surgery until milk supply and breastfeeding are established. Milk should be expressed ahead of surgery when possible. In general, when the child is healthy and full term, breastfeeding may resume, or milk may be expressed once the mother is awake and in recovery. For children who are at risk for apnea, hypotension, or hypotonia, milk may be saved for later use when the child is at lower risk (ABM [Reece-Stremtan 2017]).

Dietary Considerations

Propofol is formulated in an oil-in-water emulsion. If on parenteral nutrition, may need to adjust the amount of lipid infused. Propofol emulsion contains 1.1 kcal/mL. Soybean fat emulsion is used as a vehicle for propofol. Formulations also contain egg phospholipids (egg lecithin) and glycerol.

Monitoring Parameters

Cardiac monitor, blood pressure, oxygen saturation (during monitored anesthesia care sedation), arterial blood gas (with prolonged infusions). With prolonged infusions (eg, ICU sedation), monitor for signs and symptoms of propofol-related infusion syndrome: Metabolic acidosis, hyperkalemia, rhabdomyolysis or elevated CPK, hepatomegaly, and progression of cardiac and renal failure.

ICU sedation: Assess and adjust sedation according to scoring system (Richmond Agitation-Sedation Scale or Sedation-Agitation Scale) (SCCM [Devlin 2018]); assess CNS function daily. Serum triglyceride levels should be obtained prior to initiation of therapy and every 3 to 7 days thereafter, especially if receiving for >48 hours with doses ≥50 mcg/kg/minute (Devlin 2005); use IV port opposite propofol infusion or temporarily suspend infusion and flush port prior to blood draw.

Diprivan: Monitor zinc levels in patients predisposed to deficiency (burns, diarrhea, major sepsis) or after 5 days of treatment.

Mechanism of Action

Propofol is a short-acting, lipophilic intravenous general anesthetic. The drug is unrelated to any of the currently used barbiturate, opioid, benzodiazepine, arylcyclohexylamine, or imidazole intravenous anesthetic agents. Propofol causes global CNS depression, presumably through agonism of GABAA receptors and perhaps reduced glutamatergic activity through NMDA receptor blockade.

Pharmacokinetics

Onset of action: Anesthetic: Bolus infusion (dose dependent): 9 to 51 seconds (average 30 seconds)

Duration: 3 to 10 minutes depending on the dose, rate and duration of administration; with prolonged use (eg, 10 days ICU sedation), propofol accumulates in tissues and redistributes into plasma when the drug is discontinued, so that the time to awakening (duration of action) is increased; however, if dose is titrated on a daily basis, so that the minimum effective dose is utilized, time to awakening may be within 10 to 15 minutes even after prolonged use

Distribution: Large volume of distribution; highly lipophilic ; Vd:

Children 4 to 12 years: 5 to 10 L/kg

Adults: 2 to 10 L/kg; after a 10-day infusion, Vd approaches 60 L/kg; decreased in the elderly

Protein binding: 97% to 99%

Metabolism: Hepatic to water-soluble sulfate and glucuronide conjugates (~50%)

Half-life elimination: Biphasic: Initial: 40 minutes; Terminal: 4 to 7 hours (after 10-day infusion, may be up to 1 to 3 days)

Excretion: Urine (~88% as metabolites, 40% as glucuronide metabolite); feces (<2%)

Pharmacokinetics: Additional Considerations

Geriatric: With increasing age, the dose requirement decreases because of occurrence of higher peak plasma concentrations.

Therapeutic hypothermia: Hypothermia (33°C to 34°C or 91.4°F to 93.2°F) is associated with a decrease in total body clearance (~23%) and an increase in plasma concentrations (~28%), likely as a result of reduced hepatic blood flow and/or reduced intercompartmental clearance (Bjelland 2013; Leslie 1995). During the rewarming phase, plasma concentrations decrease (~12% or ~3% decrease for every centigrade increase in core body temperature from 33°C to 37°C [91.4°F to 98.6°F]) (Bjelland 2014).

Pricing: US

Emulsion (Diprivan Intravenous)

100 mg/10 mL (per mL): $0.14

200 mg/20 mL (per mL): $0.14

500 mg/50 mL (per mL): $0.14

1000 mg/100 mL (per mL): $0.14

Emulsion (Propofol Intravenous)

200 mg/20 mL (per mL): $0.26 - $0.36

500 mg/50 mL (per mL): $0.24 - $0.36

1000 mg/100 mL (per mL): $0.23 - $0.36

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Anefol (CL);
  • Anepol (KR, TH);
  • Anesia (HU, LK);
  • Anesticap (ID);
  • Aquafol (KR);
  • Diprivan (AE, AR, BB, BE, BF, BG, BH, BJ, BM, BR, BS, BZ, CI, CL, CN, CO, CR, CU, CY, CZ, DO, EE, EG, ES, ET, FR, GB, GH, GM, GN, GR, GT, GY, HK, HN, IE, IN, IQ, IR, IT, JM, JO, KE, KW, LB, LR, LU, LV, LY, MA, ML, MR, MT, MU, MW, MX, MY, NE, NG, NI, NL, NZ, OM, PA, PE, PH, PK, PL, PR, PT, QA, RU, SA, SC, SD, SE, SI, SK, SL, SN, SR, SV, SY, TN, TR, TT, TW, TZ, UA, UG, UY, VE, VN, YE, ZA, ZM, ZW);
  • Diprofen (TW);
  • Diprofol (IL, UA);
  • Disoprivan (CH, DE, HR);
  • Dormifor (LB);
  • Dubernard (AR);
  • Emifol (BD);
  • Fresofol (AU, CR, DO, GT, HN, KR, MY, NI, NZ, PA, PH, SV, TW);
  • Fresofol MCT/LCT (HK, ID, TH);
  • Gobbifol (AR, PY);
  • Indofol (MX);
  • Lexofol (PH);
  • Lipofol (TW);
  • Neorof (ET, PH);
  • Nirfol (LK, ZW);
  • Operol (PH);
  • Pofol (BD, EG, KR, TH);
  • Proanes (ID);
  • Profast (FI, RO);
  • Profosol (PH);
  • Propofol-Lipuro (EC);
  • Propolipid (DK, FI);
  • Propovan (LK, PY);
  • Propoven (EE, IE, LV);
  • Provive (AU, BH, HK, KR, LB, NZ, QA, ZA, ZW);
  • Recofol (AE, BH, CH, CY, ES, HU, ID, JO, MX, NL, QA, SG, TH);
  • Recofol N (MT, SG);
  • Ripol (IL);
  • Safol (ID);
  • Spiva (GR);
  • Spiva with MCT-LCT (PH);
  • Trivam (ID);
  • Troyppofol (TZ);
  • Ufol (BD);
  • Xenprof (MX)


For country abbreviations used in Lexicomp (show table)

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