Version October 2024
Dosage guidance:
Safety: Consult local/state regulations and institutional policies and procedures regarding administration and monitoring requirements prior to use; dosing practices may vary.
General anesthesia:
Note: 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 (induction): Note: May cause dose-related hypotension; consider alternative agent in patients who are hemodynamically unstable (Ref). 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 (Ref).
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) (Ref).
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 (Ref).
Monitored anesthesia care: Note: Individualize dosing based on patient factors and concomitant anesthetic agents.
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) (Ref).
or
IV: Intermittent bolus: 10 to 20 mg; may give additional doses as needed to achieve adequate sedation (Ref).
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 (Ref). Alternatively, may consider an initial dose of 0.375 to 0.75 mg/kg when combined with ketamine (as a 1:1 mixture); if needed, repeat with one-half of the initial dose (Ref).
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 (Ref). 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 (Ref).
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 (Ref).
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 (Ref).
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 (Ref).
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: No dosage adjustment necessary for any degree of kidney dysfunction (Ref).
Hemodialysis, intermittent (thrice weekly): Unlikely to be dialyzed (large Vd, highly protein bound): No supplemental dose or dosage adjustment necessary (Ref).
Peritoneal dialysis: Unlikely to be dialyzed (large Vd, highly protein bound): No dosage adjustment necessary (Ref).
CRRT: No dosage adjustment necessary (Ref).
Note: Case reports of filter clotting in patients with propofol-associated hypertriglyceridemia receiving CRRT have been reported; monitor triglycerides and visually inspect the CRRT system for evidence of congealing or a “milky brown” appearance of the “clot” as a potential cause (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (Ref).
Note: Similar concerns for a potential for filter clotting exist in patients receiving PIRRT who experience propofol-associated hypertriglyceridemia; monitor triglycerides and visually inspect the PIRRT system for evidence of congealing or a “milky brown” appearance of the “clot” as a potential cause (Ref).
No dosage adjustment necessary.
The recommendations for dosing in patients with obesity 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 (Ref). Clinicians should not change dosing weight from one weight metric to another during therapy (ie, adjusted body weight to/from actual body weight) (Ref). 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 (Ref); therefore, use of an alternative size descriptor (eg, adjusted body weight) is recommended for dosing propofol in patients with obesity (Ref). The majority of studies evaluated pharmacokinetic and pharmacodynamics of propofol when used during induction and/or maintenance of anesthesia (Ref). 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) (Ref).
Refer to adult dosing specific indications, “Debilitated or ASA-PS 3 or 4.” Smaller doses are generally required in older adults and when used with opioids. 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. Prior to use, consult local/state regulations and institutional policies and procedures regarding administration and monitoring requirements.
(For additional information see "Propofol: Pediatric drug information")
Dosage guidance:
Safety: 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.
Dosing: Dosage must be individualized based on total body weight and titrated to the desired clinical effect; the following are general dosing guidelines.
Anesthesia, general : Note: Individualize dosing based on patient factors and concomitant anesthetic agents.
Induction of general anesthesia: Children ≥3 years and Adolescents <17 years: IV: 2.5 to 3.5 mg/kg over 20 to 30 seconds. Note: Use a lower dose for ASA-PS III or IV.
Maintenance of general anesthesia: Infants ≥2 months, Children, and Adolescents:
Intermittent IV bolus: Initial: IV: 1 to 4 mg/kg once; may administer additional smaller bolus doses if clinical signs of light anesthesia present; usual bolus dose: 0.5 to 2 mg/kg/dose; repeat as needed based on clinical response and desired level of anesthesia.
Continuous IV infusion: Initial dose immediately following induction: 200 to 300 mcg/kg/minute (12 to 18 mg/kg/hour); 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). Note: Younger pediatric patients may need higher infusion rates than older pediatric patients.
ICU sedation (critically ill): Limited data available: Note: Prior to use, consult local/state regulations and institutional policies and procedures regarding administration and monitoring requirements; dosing practices may vary.
Infants, Children, and Adolescents:
Loading dose: IV: 0.5 to 1 mg/kg once; maximum dose: 50 mg/dose (Ref).
Continuous IV infusion: Usual range: 16 to 66 mcg/kg/minute (1 to 4 mg/kg/hour) (Ref). Note: Monitor closely for signs and symptoms of propofol-related infusion syndrome (PRIS).
Procedural sedation: Limited data available:
Infants, Children, and Adolescents:
Repeated IV bolus method: IV: Initial dose: 1 to 2 mg/kg; higher initial doses of 2 mg/kg are recommended in infants and children <3 years of age; follow initial dose with 0.5 to 1 mg/kg every 3 to 5 minutes as needed until adequate level of sedation achieved (Ref).
IV bolus followed by continuous IV infusion: IV: Initial bolus: 1 to 2 mg/kg followed by continuous IV infusion: Dose range: 50 to 250 mcg/kg/minute (3 to 15 mg/kg/hour); titrate to desired level of sedation (Ref).
Propofol with concurrent ketamine; emergency department procedures: IV: 0.5 to 0.75 mg/kg (Ref).
Status epilepticus; refractory: Limited data available:
Children and Adolescents:
Initial propofol infusion: IV: Loading dose 1 to 2 mg/kg once, then initiate continuous IV infusion at 20 mcg/kg/minute (1.2 mg/kg/hour); titrate to desired effect (eg, burst suppression on EEG); usual dose range: 30 to 200 mcg/kg/minute (1.8 to 12 mg/kg/hour) (Ref). Note: Use caution when administering high doses (>65 mcg/kg/minute [>3.9 mg/kg/hour]) for extended periods of time (>48 hours); monitor closely for adverse effects (eg, propofol-related infusion syndrome [PRIS]); Neurocritical Care Society guidelines for status epilepticus state that use of propofol in young children is contraindicated (Ref).
Breakthrough seizure while on propofol infusion: IV: Increase continuous IV infusion rate by 5 to 10 mcg/kg/minute (0.3 to 0.6 mg/kg/hour) every 5 minutes with or without an additional 1 mg/kg IV bolus (Ref).
There are no pediatric-specific recommendations in the manufacturer's labeling. In adults, no dosage adjustments are recommended.
There are no pediatric-specific recommendations in the manufacturer's labeling. In adults, no dosage adjustments are recommended.
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)
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 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)
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), 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
The following adverse drug reactions are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults and pediatrics.
Frequency not defined:
Cardiovascular: Acute myocardial infarction, asystole, atrial fibrillation, atrial premature contractions, atrioventricular block, bigeminy, bundle branch block, chest pain, depression of ST segment on ECG, edema, extrasystoles, flushing, hypertension, ischemic heart disease, low cardiac output, right heart failure, supraventricular tachycardia, syncope, tachycardia, ventricular fibrillation, ventricular premature contractions, ventricular tachycardia
Dermatologic: Diaphoresis, pruritus, skin rash, urticaria
Endocrine & metabolic: Dehydration, hyperglycemia, hyperkalemia, hyperlipidemia, hypomagnesemia, respiratory acidosis (during weaning), serum hyperosmolarity
Gastrointestinal: Abdominal cramps, diarrhea, hiccups, intestinal obstruction, nausea, parotid gland enlargement, sialorrhea, sore throat (burning), vomiting, xerostomia
Genitourinary: Oliguria, urinary retention
Hematologic & oncologic: Disorder of hemostatic components of blood, hemorrhage, leukocytosis
Hepatic: Abnormal liver function
Infection: Sepsis
Local: Burning sensation at injection site, erythema at injection site, injection-site phlebitis, injection-site pruritus, itching at injection site, pain at injection site (includes stinging), skin discoloration at injection site, urticaria at injection site
Nervous system: Abnormal dreams, abnormality in thinking, anticholinergic syndrome, anxiety, asthenia, atypical sexual behavior, awareness under anesthesia without pain, chills, confusion, delirium, depression, dizziness, drowsiness, emotional lability, euphoria, fatigue, hallucination, headache, hypertonia, hypotonia, hysteria, insomnia, intracranial hypertension, neuropathy, pain, paresthesia, twitching
Neuromuscular & skeletal: Laryngospasm, limb pain, muscle rigidity, myalgia, neck stiffness
Ophthalmic: Amblyopia, conjunctival hyperemia, diplopia, eye pain, nystagmus disorder, visual disturbance
Otic: Otalgia, tinnitus
Renal: Increased blood urea nitrogen, increased serum creatinine, renal failure syndrome
Respiratory: Airway obstruction, apnea, bronchospasm, cough, decreased lung function, dyspnea, hyperventilation, hypoventilation, pharyngitis, sneezing, tachypnea, wheezing
Miscellaneous: Fever
Postmarketing:
Cardiovascular: Bradycardia (Baumgarten 2021), ECG abnormality (shortening of the QT interval) (Erdil 2009), hypotension (Baumgarten 2021), phlebitis, prolonged QT interval on ECG (Kim 2008)
Endocrine & metabolic: Hypertriglyceridemia (Corrado 2020), metabolic acidosis (Chukwuemeka 2006)
Gastrointestinal: Dysgeusia (Farzana 2022), pancreatitis (Asghar 2020)
Genitourinary: Cloudy urine (including urate crystalluria) (Baumgarten 2021), urine discoloration (green) (Baumgarten 2021)
Hypersensitivity: Anaphylaxis (Koul 2011), angioedema (You 2012), infusion-related reaction (propofol-related infusion syndrome) (Krajčová 2015), nonimmune anaphylaxis (McHale 1992)
Local: Venous thrombosis at injection site
Nervous system: Altered sense of smell (Farzana 2022), anosmia (Farzana 2022), myoclonus (including perioperative; including seizure and opisthotonos) (Tam 2009), neurotoxicity (neuroexcitatory reaction [propofol “frenzy”]; including abnormal eye movements, agitation, clonus, dystonia, impaired consciousness, involuntary body movements [bucking, jerking, and thrashing], shivering, tremor) (Panchamia 2022)
Neuromuscular & skeletal: Rhabdomyolysis (Zarovnaya 2007)
Respiratory: Bronchoconstriction (Nishiyama 2001), hypoxia (Hanna 1998), pulmonary edema (Waheed 2014)
Hypersensitivity to propofol or any component of the formulation; hypersensitivity to eggs, egg products, soybeans, or soy products.
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, consider the use of an alternative anesthetic or a small trial dose of propofol prior to full dose administration (Johnson 2021).
Canadian labeling: Additional contraindication (not in US labeling): Hypersensitivity to lipid emulsions; sedation of children ≤18 years of age receiving intensive care.
Concerns related to adverse effects:
• 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.
Disease-related concerns:
• Increased intracranial pressure: Use with caution in patients with increased intracranial pressure or impaired cerebral circulation; propofol may cause substantial decreases in mean arterial pressure with subsequent decreases in cerebral perfusion pressure; to minimize risk, 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.
• 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:
• 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.
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).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
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]
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]
Generic: 1000 mg/100 mL (100 mL); 200 mg/20 mL (20 mL [DSC]); 500 mg/50 mL (50 mL)
Yes
Emulsion (Diprivan Intravenous)
100 mg/10 mL (per mL): $0.14
200 mg/20 mL (per mL): $0.36
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): $0.14 - $0.36
500 mg/50 mL (per mL): $0.14 - $0.36
1000 mg/100 mL (per mL): $0.14 - $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.
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)
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.
Note: Consult local regulations and individual institutional policies and procedures.
Parenteral: IV: 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 bolus 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 bolus doses over 20 to 30 seconds.
Maintenance: Administer at a concentration of 2 to 10 mg/mL as intermittent bolus injection at prescribed rate or as a continuous IV infusion via an infusion pump.
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.
Procedural sedation, outside the operating room; Status epilepticus, refractory
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.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (anesthetic agent, general, inhaled and IV) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care Settings).
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]).
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.
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)
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
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 QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk C: Monitor therapy
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
Arginine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Azithromycin (Systemic): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Azithromycin (Systemic). 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
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
Carbetocin: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Carbetocin. 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
Ceritinib: Propofol may enhance the bradycardic effect of Ceritinib. Propofol may enhance the QTc-prolonging 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. Also monitor for QTc prolongation and ventricular arrhythmia. 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
Chloroquine: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Chloroquine. 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
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
Clofazimine: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Clofazimine. 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
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
Dabrafenib: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Dabrafenib. 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
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
DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. 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
Domperidone: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Domperidone. Risk X: Avoid combination
Doxylamine: CNS Depressants may enhance the CNS depressant effect of Doxylamine. Risk C: Monitor therapy
DroPERidol: May enhance the CNS depressant effect of Propofol. Propofol may enhance the QTc-prolonging effect of DroPERidol. Management: Consider dose reductions of droperidol or propofol during coadministration due to additive effects on CNS depression. Also monitor for QTc prolongation and ventricular arrhythmia. Risk D: Consider therapy modification
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
Encorafenib: May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate 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
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
Etelcalcetide: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Etelcalcetide. 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
Etrasimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. 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: Propofol may enhance the arrhythmogenic effect of Fexinidazole. Propofol may enhance the QTc-prolonging 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
Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
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
Fluorouracil Products: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Fluorouracil Products. 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
Gadobenate Dimeglumine: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Gadobenate Dimeglumine. 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
Halofantrine: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Halofantrine. 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
Haloperidol: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Haloperidol. 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
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. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Iloperidone: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Inotuzumab Ozogamicin: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Inotuzumab Ozogamicin. 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
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-Foslevodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Foslevodopa. Risk C: Monitor therapy
Levoketoconazole: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Levoketoconazole. Risk X: Avoid combination
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
Lofexidine: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Lofexidine. 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
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: May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate 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
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Loxapine: CNS Depressants may enhance the CNS depressant effect of Loxapine. Risk D: Consider therapy modification
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Meglumine Antimoniate: May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate 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
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
Midostaurin: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Midostaurin. 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
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
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
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
Ondansetron: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Ondansetron. 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
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
Oxytocin: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Oxytocin. 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
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
Pentamidine (Systemic): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Pentamidine (Systemic). 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
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
Pimozide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
Piperaquine: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Piperaquine. 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
Probucol: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Probucol. 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
Procarbazine: May enhance the CNS depressant effect of CNS Depressants. 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): Propofol may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QT-prolonging Antidepressants (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate 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
QT-prolonging Antipsychotics (Moderate Risk): May enhance the QTc-prolonging effect of Propofol. 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
QT-prolonging Class IC Antiarrhythmics (Moderate Risk): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Class IC Antiarrhythmics (Moderate 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
QT-Prolonging Inhalational Anesthetics (Moderate Risk): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of QT-Prolonging Inhalational Anesthetics (Moderate 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
QT-prolonging Kinase Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate 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
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Miscellaneous Agents (Moderate 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
QT-prolonging Quinolone Antibiotics (Moderate Risk): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Quinolone Antibiotics (Moderate 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
QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of Propofol. 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
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
Sertindole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
Silodosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. 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
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
Toremifene: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Toremifene. 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
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. Management: Decrease the propofol dose and monitor for sedation and cardiorespiratory depression during coadministration with valproate products. Risk D: Consider therapy modification
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
Zuranolone: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider therapy modification
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.
Propofol crosses the placenta and may be associated with neonatal CNS and respiratory depression. Monitor exposed neonates for hypotonia and sedation.
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 has been used as an induction agent in cases where general anesthesia is needed for cesarean delivery (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).
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).
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. The Academy of Breastfeeding 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]).
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.
Cardiac monitor, BP, 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 and/or 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.
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.
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%)
Older adult: 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).
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