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    Other General Anesthetics

    DEA CLASS

    Rx

    DESCRIPTION

    Intravenous general anesthetic and sedative
    Used for general anesthesia induction and maintenance, monitored anesthesia care (MAC) sedation, combined sedation and regional anesthesia, and intensive care unit (ICU) sedation of mechanically ventilated patients
    Prolonged, high-dose infusions for ICU sedation associated with metabolic derangements and organ system failures, referred to as propofol-related infusion syndrome (PRIS)

    COMMON BRAND NAMES

    Diprivan, Fresenius Propoven

    HOW SUPPLIED

    Diprivan/Fresenius Propoven/Propofol Intravenous Inj Emulsion: 1mL, 10mg, 20mg

    DOSAGE & INDICATIONS

    For general anesthesia induction.
    For cardiac anesthesia.
    Intravenous dosage
    Adults

    0.5 to 1.5 mg/kg IV until induction onset as determined by clinical response of the patient.

    Adolescents 17 years

    0.5 to 1.5 mg/kg IV until induction onset as determined by clinical response of the patient.

    For neurosurgical anesthesia.
    Intravenous dosage
    Adults

    1 to 2 mg/kg IV until induction onset as determined by clinical response of the patient.

    Adolescents 17 years

    1 to 2 mg/kg IV until induction onset as determined by clinical response of the patient.

    Intravenous dosage
    Adults 18 to 64 years classified as ASA-PS I or II

    2 to 2.5 mg/kg IV until induction onset as determined by clinical response of the patient.

    Geriatric or Debilitated Adults or Adults classified as ASA-PS III or IV

    1 to 1.5 mg/kg IV until induction onset as determined by clinical response of the patient.

    Adolescents 17 years classified as ASA-PS I or II

    2 to 2.5 mg/kg IV until induction onset as determined by clinical response of the patient.

    Debilitated Adolescents 17 years or Adolescents 17 years classified as ASA-PS III or IV

    1 to 1.5 mg/kg IV until induction onset as determined by clinical response of the patient.

    Children and Adolescents 3 to 16 years

    2.5 to 3.5 mg/kg IV until induction onset in healthy patients (ASA-PS I or II). Use a lower dose in patients with severe systemic disease (ASA-PS III or IV). Young pediatric patients may require higher doses within this dosage range compared to older pediatric patients.[31036] [54857] [54858]

    For general anesthesia maintenance.
    For cardiac anesthesia.
    Continuous Intravenous Infusion dosage
    Adults

    25 to 100 mcg/kg/minute continuous IV infusion immediately after induction. Titrate to clinical response.

    Adolescents 17 years

    25 to 100 mcg/kg/minute continuous IV infusion immediately after induction. Titrate to clinical response.

    For neurosurgical anesthesia.
    Continuous Intravenous Infusion dosage
    Adults

    100 to 200 mcg/kg/minute continuous IV infusion immediately after induction. Titrate to clinical response.

    Adolescents 17 years

    100 to 200 mcg/kg/minute continuous IV infusion immediately after induction. Titrate to clinical response.

    Intermittent Intravenous dosage
    Adults 18 to 64 years classified as ASA-PS I or II

    20 to 50 mg IV as needed when changes in vital signs indicate a response to surgical stimulation or light anesthesia.[31036]

    Adolescents 17 years classified as ASA-PS I or II

    20 to 50 mg IV as needed when changes in vital signs indicate a response to surgical stimulation or light anesthesia.[31036]

    Infants, Children, and Adolescents 2 months to 16 years

    1 to 4 mg/kg IV with an additional 0.5 to 2 mg/kg/dose as needed when changes in vital signs indicate a response to surgical stimulation or light anesthesia.[31036]

    Continuous Intravenous Infusion dosage
    Adults 18 to 64 years classified as ASA-PS I or II

    150 to 200 mcg/kg/minute continuous IV infusion for 10 to 15 minutes immediately after induction. Decrease infusion rate by 30% to 50% during the first 30 minutes of maintenance. Titrate to clinical response. Usual dose: 50 to 100 mcg/kg/minute.

    Geriatric or Debilitated Adults or Adults classified as ASA-PS III or IV

    50 to 100 mcg/kg/minute continuous IV infusion immediately after induction. Titrate to clinical response.

    Adolescents 17 years classified as ASA-PS I or II

    150 to 200 mcg/kg/minute continuous IV infusion for 10 to 15 minutes immediately after induction. Decrease infusion rate by 30% to 50% during the first 30 minutes of maintenance. Titrate to clinical response. Usual dose: 50 to 100 mcg/kg/minute.

    Debilitated Adolescents 17 years or Adolescents 17 years classified as ASA-PS III or IV

    50 to 100 mcg/kg/minute continuous IV infusion immediately after induction. Titrate to clinical response.

    Infants, Children, and Adolescents 2 months to 16 years

    200 to 300 mcg/kg/minute continuous IV infusion immediately after induction. Decrease infusion rate to 125 to 150 mcg/kg/minute after 30 minutes if clinical signs of light anesthesia are not present. Titrate to clinical response. Use a lower dose in patients with severe systemic disease (ASA-PS III or IV). Young pediatric patients may require higher doses within this dosage range compared to older pediatric patients.

    For monitored anesthesia care sedation.
    Intermittent Intravenous dosage

    NOTE: A variable infusion rate technique is preferred over intermittent bolus technique for maintenance of MAC sedation. With the intermittent bolus method of sedation maintenance, there is increased potential for respiratory depression, transient increases in sedation depth, and prolongation of recovery.[31036]

    Adults

    0.5 mg/kg IV over 3 to 5 minutes, followed by 10 to 20 mg IV as needed. Titrate to clinical response. Reduce the dose to approximately 80% of the usual dose and avoid rapid bolus doses in elderly, debilitated, or neurosurgical patients or patients classified as ASA-PS III or IV according to their condition, responses, and changes in vital signs.[31036]

    Adolescents 17 years

    0.5 mg/kg IV over 3 to 5 minutes, followed by 10 to 20 mg IV as needed. Titrate to clinical response. Reduce the dose to approximately 80% of the usual dose and avoid rapid bolus doses in debilitated or neurosurgical patients or patients classified as ASA-PS III or IV according to their condition, responses, and changes in vital signs.[31036]

    Continuous Intravenous Infusion dosage
    Adults

    0.5 mg/kg IV over 3 to 5 minutes or 100 to 150 mcg/kg/minute continuous IV infusion for 3 to 5 minutes, followed by 25 to 75 mcg/kg/minute continuous IV infusion for the next 10 to 15 minutes, and then 25 to 50 mcg/kg/minute continuous IV infusion. Titrate approximately every 2 minutes to clinical response. Reduce the dose to approximately 80% of the usual dose in elderly, debilitated, or neurosurgical patients or patients classified as ASA-PS III or IV according to their condition, responses, and changes in vital signs.[31036]

    Adolescents 17 years

    0.5 mg/kg IV over 3 to 5 minutes or 100 to 150 mcg/kg/minute continuous IV infusion for 3 to 5 minutes, followed by 25 to 75 mcg/kg/minute continuous IV infusion for the next 10 to 15 minutes, and then 25 to 50 mcg/kg/minute continuous IV infusion. Titrate approximately every 2 minutes to clinical response. Reduce the dose to approximately 80% of the usual dose in debilitated or neurosurgical patients or patients classified as ASA-PS III or IV according to their condition, responses, and changes in vital signs.

    For sedation induction and sedation maintenance of mechanically ventilated intensive care patients.
    Intravenous dosage
    Adults

    5 mcg/kg/minute continuous IV infusion, initially; titrate by 5 to 10 mcg/kg/minute every 5 to 10 minutes to clinical response. Usual dose: 5 to 50 mcg/kg/minute. Do not exceed 4 mg/kg/hour unless the benefits outweigh the risks. May use 10 to 20 mg IV bolus if needed to rapidly increase sedation depth in patients where hypotension is unlikely to occur.[31036] [57161] Guidelines recommend nonbenzodiazepine sedatives over benzodiazepines for sedation in critically ill, mechanically ventilated patients.[65297]

    Adolescents 17 years

    5 mcg/kg/minute continuous IV infusion, initially; titrate by 5 to 10 mcg/kg/minute every 5 to 10 minutes to clinical response. Usual dose: 5 to 50 mcg/kg/minute. Do not exceed 4 mg/kg/hour unless the benefits outweigh the risks. May use 10 to 20 mg IV bolus if needed to rapidly increase sedation depth in patients where hypotension is unlikely to occur.[31036] [57161]

    For procedural sedation†.
    Intermittent Intravenous dosage
    Infants, Children, and Adolescents

    0.5 to 1.5 mg/kg IV, followed by 0.25 to 0.5 mg/kg/dose IV every 3 to 5 minutes as needed. Titrate to clinical response.

    Continuous Intravenous Infusion dosage
    Infants, Children, and Adolescents

    0.5 to 1.5 mg/kg IV, followed by 50 to 200 mcg/kg/minute continuous IV infusion. Titrate to clinical response.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Specific maximum dosage information is not available. Dosage must be individualized based on clinical response.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed. The long-term administration of propofol to patients with hepatic insufficiency has not been evaluated.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed. The long-term administration of propofol to patients with renal failure has not been evaluated.

    ADMINISTRATION

     
    Propofol administration requires an experienced clinician. For general anesthesia or monitored anesthesia care (MAC) sedation, propofol should be administered only by persons trained in the administration of general anesthesia and not involved in the conduct of the surgical or diagnostic procedure. For sedation of intubated, mechanically ventilated patients in the intensive care unit, propofol should be administered only by persons skilled in the management of critically ill patients and trained in cardiovascular resuscitation and airway management.
    Facilities for maintenance of a patent airway, providing artificial ventilation, administering supplemental oxygen, and instituting cardiovascular resuscitation must be immediately available. Continuously monitor sedated patients for early signs of hypotension, apnea, airway obstruction, and/or oxygen desaturation.[31036]
    There is a potential for overdose with Fresenius Propoven 2%, which the FDA has permitted for emergency use under an Emergency Use Authorization (EUA). Fresenius Propoven 2% (propofol 20 mg/mL) is double the concentration of FDA-approved propofol 1% (propofol 10 mg/mL). Exercise caution and implement steps to ensure dosing calculations, infusion rates, and infusion pump settings are accurate.[65407]
    Store and manage propofol inventory to prevent the risk of diversion, including restriction of access and accounting procedures as appropriate to the clinical setting.[31036]

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Do not use if there is evidence of excessive creaming or aggregation, if large droplets are visible, or if other forms of phase separation are evident. Slight creaming, which should disappear after shaking, may be visible upon prolonged standing.
    Shake well before use.
    Strict aseptic technique must always be maintained during handling. Propofol is a single access parenteral product (single patient infusion vial); propofol vials are never to be accessed more than once or used on more than 1 person.[31036]

    Intravenous Administration

    Prepare propofol for use just before initiation of each anesthetic or sedative procedure.
    Disinfect the vial rubber stopper using 70% isopropyl alcohol.
    Individualize doses and rates of administration and titrate to clinical response. Allow an adequate interval (i.e., 3 to 5 minutes) between dose adjustments to assess clinical effects.
    Flush the IV line every 12 hours and at the end of the anesthetic or sedative procedure to remove residual propofol.
    Do not mix propofol with other medications before administration. If lidocaine is to be administered to minimize pain on injection of propofol, it is recommended that it be administered before propofol administration or that it be added to propofol immediately before administration and in quantities not exceeding 20 mg lidocaine/200 mg propofol.
    Clinical experience with the use of in-line filters and propofol is limited. Only administer propofol through a filter with a pore size of 5 micron or more unless it has been demonstrated that the filter does not restrict the flow of propofol and/or cause the breakdown of the emulsion. Use filters with caution and where clinically appropriate. Continuous monitoring is necessary due to the potential for restricted flow and/or breakdown of the emulsion.[31036] Do not administer Fresenius Propoven via a microbiological filter.[54849]
    Storage: Discard any unused propofol, reservoirs, dedicated administration tubing and/or solutions containing propofol at the end of the anesthetic or sedative procedure or at 12 hours, whichever occurs sooner. Any propofol and lidocaine mixture must be administered within 6 hours of preparation.[31036] [54849] [55029]
     
    Dilution
    Propofol is provided as a ready-to-use formulation. However, should dilution be necessary, propofol may only be diluted with 5% Dextrose Injection, and it should not be diluted to a concentration of less than 2 mg/mL because it is an emulsion. In diluted form, it is more stable when in contact with glass than with plastic (95% potency after 2 hours of running infusion in plastic).[31036]
     
    Intermittent IV Injection
    Withdraw propofol into a sterile syringe immediately after a vial is opened. When withdrawing propofol from vials, use a sterile vent spike. Label the syringe with appropriate information, including the date and time the vial was opened.
    To minimize pain on injection when administering propofol to pediatric patients, boluses may be administered via antecubital fossa or larger veins of the forearm or small veins if pretreated with lidocaine. Pain during intravenous injection may be reduced by prior injection of IV lidocaine (1 mL of a 1% solution). It is recommended that lidocaine be administered before propofol administration or that it be added to propofol immediately before administration and in quantities not exceeding 20 mg lidocaine/200 mg propofol.
    During initiation of monitored anesthesia care (MAC) sedation, slow infusion or slow injection techniques are preferable over rapid bolus administration. During maintenance of MAC sedation, a variable rate infusion is preferable over intermittent bolus dose administration.[31036]
     
    Continuous IV Infusion
    ASHP Recommended Standard Concentrations for Adult Continuous Infusions: 10 mg/mL.[64020]
    ASHP Recommended Standard Concentrations for Pediatric Continuous Infusions: 10 mg/mL.
    When administering propofol by infusion, syringe or volumetric pumps are recommended to provide controlled infusion rates. When infusing propofol to patients undergoing magnetic resonance imaging, metered control devices may be utilized if mechanical pumps are impractical.
    Use a sterile vent spike and sterile tubing for propofol administration. As with other lipid emulsions, minimize the number of IV line manipulations.
    Titrate infusion rates downward in the absence of clinical signs of light anesthesia until a mild response to stimulation is obtained to avoid administration of propofol at rates higher than are clinically necessary.
    Avoid abrupt discontinuation of propofol before weaning or for daily evaluation of sedation levels. This may result in rapid awakening with associated anxiety, agitation, and resistance to mechanical ventilation. Maintain a light level of sedation throughout the weaning process until 10 to 15 minutes before extubation, at which time the propofol infusion can be discontinued.[31036]

    STORAGE

    Diprivan:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Discard vial after 12 hours
    - Do not freeze
    - Store between 40 to 77 degrees F
    Fresenius Propoven :
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Discard vial after 12 hours
    - Do not freeze
    - Store between 40 to 77 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Asthma, egg hypersensitivity, peanut hypersensitivity, soya lecithin hypersensitivity, sulfite hypersensitivity

    Propofol is contraindicated in patients with a known hypersensitivity to propofol or to any of the components, which include soybean oil and egg phospholipid; therefore, propofol is also contraindicated in patients with egg hypersensitivity or soya lecithin hypersensitivity. Fresenius Propoven is also contraindicated in patients with peanut hypersensitivity.[31036] [60725] [65407] Certain formulations of propofol contain sodium metabisulfite. Sodium metabisulfite is a sulfite that may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe episodes in certain susceptible people, such as patients with sulfite hypersensitivity or asthma.[55029]

    Cardiac disease, hypovolemia, sepsis

    When using propofol for cardiac anesthesia in patients with cardiac disease, use slower rates of administration in premedicated patients, elderly patients, patients with recent fluid shifts, and patients who are hemodynamically unstable. Patients with compromised myocardial function, intravascular volume depletion, or abnormally low vascular tone (e.g., sepsis) may be more susceptible to hypotension. Correct hypovolemia before administration of propofol. In those patients where additional fluid therapy may be contraindicated, other measures, such as elevation of lower extremities or use of pressor agents, may be useful to offset the hypotension which is associated with the induction of anesthesia with propofol. When propofol is used as the primary cardiac anesthetic, it should not be administered with the high-dose opioid technique, as this may increase the likelihood of hypotension.[31036]

    Hyperlipidemia, hyperlipoproteinemia, pancreatitis

    Use propofol with caution in patients with disorders of lipid metabolism, such as primary hyperlipoproteinemia, diabetic hyperlipemia, and pancreatitis. Monitor patients at risk for hyperlipidemia for increases in serum triglycerides or serum turbidity. Since propofol is formulated in an oil-in-water emulsion, elevations in serum triglycerides may occur when propofol is administered for extended periods. Adjust propofol administration if fat is being inadequately cleared from the body. A reduction in the quantity of concurrently administered lipids is indicated to compensate for the amount of lipid infused as part of the propofol formulation. When used for intensive care unit sedation, individualize the propofol dose according to the patient's condition and response, blood lipid profile, and vital signs.[31036]

    Cerebrovascular disease, increased intracranial pressure, seizure disorder

    When propofol is used in patients with increased intracranial pressure (ICP) or impaired cerebral circulation (cerebrovascular disease), avoid significant decreases in mean arterial pressure because of the resultant decreases in cerebral perfusion pressure. To avoid significant hypotension and decreases in cerebral perfusion pressure, use an infusion or slow bolus instead of rapid, more frequent, and/or larger boluses of propofol. Slower induction, titrated to clinical responses, will generally result in reduced induction dosage requirements. When increased ICP is suspected, hyperventilation and hypocarbia should accompany propofol administration. Also, when propofol is administered to a patient with a seizure disorder, there is a risk of seizure during the recovery phase.[31036]

    Geriatric

    Use a lower induction dose and a slower maintenance rate of administration of propofol in geriatric patients. Do not use rapid (single or repeated) bolus administration to minimize undesirable cardiorespiratory depression.[31036]

    Burns, diarrhea

    Consider zinc supplementation during prolonged therapy with propofol for patients predisposed to zinc deficiency, including those with burns, diarrhea, or sepsis. Do not infuse propofol for more than 5 days without providing a drug holiday to safely replace estimated or measured urine zinc losses. Certain formulations of propofol (e.g., Diprivan) contain ethylenediaminetetraacetic acid (EDTA), which is a strong chelator of trace metals including zinc.

    Renal failure, renal impairment

    In patients at risk for renal impairment, monitor urinalysis and urine sediment before starting propofol and on alternate days during therapy. At high doses (2 to 3 g/day), ethylenediaminetetraacetic acid (EDTA) has been reported, on rare occasions, to be toxic to the renal tubules. Certain formulations of propofol (e.g., Diprivan) contain EDTA. The long-term administration of propofol to patients with renal failure has not been evaluated.[31036]

    Driving or operating machinery

    Advise patients that performance of activities requiring mental alertness, such as driving or operating machinery, may be impaired for some time after general anesthesia or sedation with propofol.

    Brain tumor, children, corticosteroid therapy, head trauma, infants, neonates, premature neonates, stroke

    Certain formulations of propofol contain benzyl alcohol. Excessive amounts of benzyl alcohol in neonates have been associated with hypotension, metabolic acidosis, and kernicterus. A "gasping syndrome" characterized by CNS depression, metabolic acidosis, and gasping respirations has been associated with benzyl alcohol dosages more than 99 mg/kg/day in neonates. The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known. Consider the daily metabolic load of benzyl alcohol from combined sources. Premature neonates and low-birth-weight neonates may be more likely to develop toxicity. Repeated or lengthy use of general anesthetic and sedation drugs during surgeries or procedures in neonates, infants, and children younger than 3 years, including in utero exposure during the third trimester, may have negative effects on brain development. Consider the benefits of appropriate anesthesia in young children against the potential risks, especially for procedures that may last more than 3 hours or if multiple procedures are required during the first 3 years of life. It may be appropriate to delay certain procedures if doing so will not jeopardize the health of the child. No specific anesthetic or sedation drug has been shown to be safer than another. Human studies suggest that a single short exposure to a general anesthetic in young pediatric patients is unlikely to have negative effects on behavior and learning; however, further research is needed to fully characterize how anesthetic exposure affects brain development.[61572] Propofol is not recommended for sedation of patients younger than 17 years in the pediatric intensive care unit (PICU). An increased number of deaths was observed in a randomized controlled trial of PICU patients (n = 327) who received propofol compared to those who received standard sedative agents (e.g., lorazepam, chloral hydrate, fentanyl, ketamine, morphine, phenobarbital) for sedation. Of the patients that died, 11% were in the propofol 2% group, 8% were in the propofol 1% group, and 4% were in the standard sedative group. Careful review of the deaths failed to reveal a correlation with underlying disease status or a definite pattern to the causes of death. However, the use of propofol for PICU sedation has been associated with propofol-related infusion syndrome, a constellation of effects characterized by severe metabolic acidosis, hyperkalemia, lipemia, rhabdomyolysis, hepatomegaly, renal failure, cardiac failure, and/or ECG changes similar to those seen in the Brugada syndrome. Risk factors for the development of these events include decreased oxygen delivery to tissues, serious neurological injury (e.g., head trauma, brain tumor, stroke), sepsis, high dosages of concomitant vasoconstrictors, corticosteroid therapy, or inotropes, and high-dose infusions of propofol (more than 5 mg/kg/hour [83 mcg/kg/minute] for more than 48 hours). The syndrome has also been reported with high-dose, short-term infusions of propofol during surgical anesthesia. The mechanism of these effects is not fully understood, and although the syndrome can occur in both pediatric and adult patients, it appears to be more common in the pediatric population. Therefore, avoid PICU sedation with propofol and consider alternative sedation for any patient who requires prolonged sedation or increasing propofol dosage. Monitor creatinine kinase, myoglobin, and blood lactate if prolonged propofol infusions are used. If metabolic acidosis occurs during use of propofol for any indication, immediately discontinue the drug and do not rechallenge the patient.[26920] [26921] [31036] [55022] [55035] [55036] [55076]

    Abrupt discontinuation

    Avoid abrupt discontinuation of propofol before weaning or for daily evaluation of sedation levels. This may result in rapid awakening with associated anxiety, agitation, and resistance to mechanical ventilation. Maintain a light level of sedation throughout the weaning process until 10 to 15 minutes before extubation, at which time the propofol infusion can be discontinued. In pediatric patients, abrupt discontinuation of propofol after prolonged infusion may result in flushing of the hands and feet, agitation, tremulousness, and hyperirritability.[31036]

    Potential for overdose or poisoning, requires a specialized care setting, requires an experienced clinician

    Propofol administration requires an experienced clinician and requires a specialized care setting. For general anesthesia or monitored anesthesia care (MAC) sedation, propofol should be administered only by persons trained in the administration of general anesthesia and not involved in the conduct of the surgical or diagnostic procedure. For sedation of intubated, mechanically ventilated patients in the intensive care unit, propofol should be administered only by persons skilled in the management of critically ill patients and trained in cardiovascular resuscitation and airway management. Facilities for maintenance of a patent airway, providing artificial ventilation, administering supplemental oxygen, and instituting cardiovascular resuscitation must be immediately available. Continuously monitor sedated patients for early signs of hypotension, apnea, airway obstruction, and/or oxygen desaturation. These cardiorespiratory effects are more likely to occur after rapid bolus administration, especially in the elderly, debilitated, or ASA-PS III or IV patients.[31036] There is a potential for overdose or poisoning with Fresenius Propoven 2%, which the FDA has permitted for emergency use under an Emergency Use Authorization (EUA). Fresenius Propoven 2% (propofol 20 mg/mL) is double the concentration of FDA-approved propofol 1% (propofol 10 mg/mL). Exercise caution and implement steps to ensure dosing calculations, infusion rates, and infusion pump settings are accurate.[65407] Store and manage propofol inventory to prevent the risk of diversion, including restriction of access and accounting procedures as appropriate to the clinical setting. There are reports of the abuse of propofol for recreational and other improper purposes, which have resulted in fatalities and other injuries. Instances of self-administration of propofol by health care professionals have also been reported, which have resulted in fatalities and other injuries.[31036]

    Labor, obstetric delivery, pregnancy

    There are no adequate and well-controlled studies of propofol use in pregnant women. In animal reproduction studies, increased implantation losses and decreased pup survival were reported at propofol exposures at or less than the human induction dose before mating and during early gestation or during late gestation.[31036] Repeated or lengthy use of general anesthetic and sedation drugs during surgeries or procedures during the third trimester of pregnancy may have negative effects on fetal brain development. Consider the benefits of appropriate anesthesia in pregnant women against the potential risks, especially for procedures that may last more than 3 hours or if multiple procedures are required prior to delivery. It may be appropriate to delay certain procedures if doing so will not jeopardize the health of the child and/or mother. No specific anesthetic or sedation drug has been shown to be safer than another. Human studies suggest that a single short exposure to a general anesthetic in young pediatric patients is unlikely to have negative effects on behavior and learning; however, further research is needed to fully characterize how anesthetic exposure affects brain development.[61572] Propofol is not recommended for labor and obstetric delivery, including cesarean section deliveries, because the drug crosses the placenta and may be associated with neonatal depression.[31036] The FDA issued an Emergency Use Authorization (EUA) permitting the emergency use of Fresenius Propoven 2%; do not use Fresenius Propoven 2% in pregnant women unless there are no FDA-approved products available to maintain sedation for these patients who require mechanical ventilation in an intensive care unit setting.[65407]

    Breast-feeding

    Propofol is excreted in human milk. Variable concentrations in human milk have been reported with administration of propofol to breast-feeding mothers in the postpartum period. Adverse reactions in breastfed infants have not been reported. The effects of propofol on human milk production are unknown.[31036] Some experts state that in general, healthy term infants can safely nurse after a surgical procedure, as soon as the mother is awake and alert.[28006] [48668] Propofol is minimally excreted in breast milk, and the oral bioavailability to a nursing infant is likely to be very low. In a study of 5 women (6 to 15 weeks postpartum) given a single dose of propofol 2.5 mg/kg, milk samples collected 5 to 24 hours after injection indicate that an infant would receive approximately 0.0052 mg/kg (or 0.2% of the maternal weight-adjusted dose) in the 24 hours after the dose.[62842] [62843] The effects of oral propofol ingestion by an infant are unknown, but it appears that the risk of infant exposure to the drug is low.[28006]

    ADVERSE REACTIONS

    Severe

    bradycardia / Rapid / 1.0-3.0
    apnea / Delayed / 1.0-3.0
    ventricular tachycardia / Early / 0-1.0
    heart failure / Delayed / 0-1.0
    atrial fibrillation / Early / 0-1.0
    cardiac arrest / Early / 0-1.0
    myocardial infarction / Delayed / 0-1.0
    AV block / Early / 0-1.0
    ventricular fibrillation / Early / 0-1.0
    increased intracranial pressure / Early / 0-1.0
    seizures / Delayed / 0-1.0
    thrombosis / Delayed / 0-1.0
    bronchospasm / Rapid / 0-1.0
    anaphylactoid reactions / Rapid / 0-1.0
    laryngospasm / Rapid / 0-1.0
    hyperkalemia / Delayed / 0-1.0
    ileus / Delayed / 0-1.0
    renal failure (unspecified) / Delayed / 0-1.0
    oliguria / Early / 0-1.0
    pulmonary edema / Early / Incidence not known
    tissue necrosis / Early / Incidence not known
    angioedema / Rapid / Incidence not known
    propofol-related infusion syndrome / Delayed / Incidence not known
    pancreatitis / Delayed / Incidence not known

    Moderate

    hypotension / Rapid / 3.0-26.0
    hypertension / Early / 0-8.0
    sinus tachycardia / Rapid / 0-3.0
    bundle-branch block / Early / 0-1.0
    edema / Delayed / 0-1.0
    premature ventricular contractions (PVCs) / Early / 0-1.0
    supraventricular tachycardia (SVT) / Early / 0-1.0
    chest pain (unspecified) / Early / 0-1.0
    tachypnea / Early / 0-1.0
    hypoxia / Early / 0-1.0
    dyspnea / Early / 0-1.0
    hypoventilation / Rapid / 0-1.0
    wheezing / Rapid / 0-1.0
    euphoria / Early / 0-1.0
    confusion / Early / 0-1.0
    depression / Delayed / 0-1.0
    delirium / Early / 0-1.0
    myoclonia / Delayed / 0-1.0
    hallucinations / Early / 0-1.0
    dystonic reaction / Delayed / 0-1.0
    hypotonia / Delayed / 0-1.0
    hypertonia / Delayed / 0-1.0
    phlebitis / Rapid / 0-1.0
    metabolic acidosis / Delayed / 0-1.0
    amblyopia / Delayed / 0-1.0
    conjunctival hyperemia / Early / 0-1.0
    nystagmus / Delayed / 0-1.0
    urinary retention / Early / 0-1.0
    bleeding / Early / 0-1.0
    dehydration / Delayed / 0-1.0
    hypomagnesemia / Delayed / 0-1.0
    hyperglycemia / Delayed / 0-1.0
    respiratory depression / Rapid / Incidence not known
    erythema / Early / Incidence not known
    hypertriglyceridemia / Delayed / Incidence not known
    zinc deficiency / Delayed / Incidence not known

    Mild

    injection site reaction / Rapid / 10.0-17.6
    rash / Early / 0-5.0
    pruritus / Rapid / 0-2.0
    premature atrial contractions (PACs) / Early / 0-1.0
    syncope / Early / 0-1.0
    hyperventilation / Early / 0-1.0
    cough / Delayed / 0-1.0
    pharyngitis / Delayed / 0-1.0
    hiccups / Early / 0-1.0
    sneezing / Early / 0-1.0
    agitation / Early / 0-1.0
    insomnia / Early / 0-1.0
    fatigue / Early / 0-1.0
    drowsiness / Early / 0-1.0
    paresthesias / Delayed / 0-1.0
    headache / Early / 0-1.0
    tremor / Early / 0-1.0
    emotional lability / Early / 0-1.0
    anxiety / Delayed / 0-1.0
    shivering / Rapid / 0-1.0
    abnormal dreams / Early / 0-1.0
    flushing / Rapid / 0-1.0
    diaphoresis / Early / 0-1.0
    urticaria / Rapid / 0-1.0
    chills / Rapid / 0-1.0
    fever / Early / 0-1.0
    diarrhea / Early / 0-1.0
    xerostomia / Early / 0-1.0
    nausea / Early / 0-1.0
    hypersalivation / Early / 0-1.0
    vomiting / Early / 0-1.0
    diplopia / Early / 0-1.0
    ocular pain / Early / 0-1.0
    dysgeusia / Early / 0-1.0
    tinnitus / Delayed / 0-1.0
    urine discoloration / Early / 0-1.0
    leukocytosis / Delayed / 0-1.0
    myalgia / Early / 0-1.0
    asthenia / Delayed / 0-1.0
    weakness / Early / 0-1.0
    infection / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Aspirin; Diphenhydramine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Acetaminophen; Caffeine; Dihydrocodeine: (Major) Concomitant use of dihydrocodeine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Acetaminophen; Caffeine; Pyrilamine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Acetaminophen; Chlorpheniramine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Acetaminophen; Chlorpheniramine; Dextromethorphan: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Initially, vasopressors may reduce propofol serum concentrations due to increased metabolic clearance secondary to increased hepatic blood flow. An increase in the propofol dose may be required. Additionally, the vasopressor dose may need to be increased over time due to tachyphylaxis. Thus, these drugs may drive each other in a progressively myocardial depressive loop, which could lead to cardiac arrhythmias or cardiac failure. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Initially, vasopressors may reduce propofol serum concentrations due to increased metabolic clearance secondary to increased hepatic blood flow. An increase in the propofol dose may be required. Additionally, the vasopressor dose may need to be increased over time due to tachyphylaxis. Thus, these drugs may drive each other in a progressively myocardial depressive loop, which could lead to cardiac arrhythmias or cardiac failure. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Acetaminophen; Codeine: (Major) Concomitant use of codeine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Acetaminophen; Dextromethorphan; Doxylamine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Initially, vasopressors may reduce propofol serum concentrations due to increased metabolic clearance secondary to increased hepatic blood flow. An increase in the propofol dose may be required. Additionally, the vasopressor dose may need to be increased over time due to tachyphylaxis. Thus, these drugs may drive each other in a progressively myocardial depressive loop, which could lead to cardiac arrhythmias or cardiac failure.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Initially, vasopressors may reduce propofol serum concentrations due to increased metabolic clearance secondary to increased hepatic blood flow. An increase in the propofol dose may be required. Additionally, the vasopressor dose may need to be increased over time due to tachyphylaxis. Thus, these drugs may drive each other in a progressively myocardial depressive loop, which could lead to cardiac arrhythmias or cardiac failure.
    Acetaminophen; Diphenhydramine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Initially, vasopressors may reduce propofol serum concentrations due to increased metabolic clearance secondary to increased hepatic blood flow. An increase in the propofol dose may be required. Additionally, the vasopressor dose may need to be increased over time due to tachyphylaxis. Thus, these drugs may drive each other in a progressively myocardial depressive loop, which could lead to cardiac arrhythmias or cardiac failure.
    Acetaminophen; Hydrocodone: (Major) Concomitant use of hydrocodone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Acetaminophen; Oxycodone: (Major) Concomitant use of oxycodone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Acetaminophen; Pamabrom; Pyrilamine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Acrivastine; Pseudoephedrine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Aliskiren: (Moderate) General anesthtics may be associated with hypotension; however the frequency is less than with inhalational anesthetic agents. Concomitant use with aliskiren may increase the risk of developing hypotension.
    Aliskiren; Amlodipine: (Moderate) General anesthtics may be associated with hypotension; however the frequency is less than with inhalational anesthetic agents. Concomitant use with aliskiren may increase the risk of developing hypotension.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) General anesthtics may be associated with hypotension; however the frequency is less than with inhalational anesthetic agents. Concomitant use with aliskiren may increase the risk of developing hypotension.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) General anesthtics may be associated with hypotension; however the frequency is less than with inhalational anesthetic agents. Concomitant use with aliskiren may increase the risk of developing hypotension.
    Aliskiren; Valsartan: (Moderate) General anesthtics may be associated with hypotension; however the frequency is less than with inhalational anesthetic agents. Concomitant use with aliskiren may increase the risk of developing hypotension.
    Ambrisentan: (Minor) General anesthtics may be associated with hypotension; however the frequency is less than with inhalational anesthetic agents. Concomitant use with ambrisentan may increase the risk of developing hypotension.
    Amikacin: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving amikacin.
    Amiodarone: (Major) In general, adverse cardiovascular effects such as hypotension and atropine-resistant bradycardia can occur in patients receiving amiodarone who subsequently are administered any general anesthetics, particularly volatile anesthetics. Due to the extremely long half-life of amiodarone, a drug interaction is also possible for days to weeks after discontinuation of amiodarone. For example, when fentanyl was administered to patients receiving amiodarone, the incidence of bradycardia and other adverse cardiovascular effects was much higher than in patients not on amiodarone who received fentanyl.
    Amitriptyline: (Moderate) General anesthetics like propofol may produce additive CNS depression when used in patients taking tricyclic antidepressants.
    Amobarbital: (Moderate) Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
    Amoxapine: (Moderate) Because amoxapine can cause sedation, an enhanced CNS depressant effect may occur during combined use with general anesthetics such as enflurane.
    Amphetamine: (Major) Inhalational general anesthetics may sensitize the myocardium to the effects of dextroamphetamine. Dosages of the amphetamines should be substantially reduced prior to surgery, and caution should be observed with concurrent use of anesthetics.
    Amphetamine; Dextroamphetamine Salts: (Major) Inhalational general anesthetics may sensitize the myocardium to the effects of dextroamphetamine. Dosages of the amphetamines should be substantially reduced prior to surgery, and caution should be observed with concurrent use of anesthetics.
    Amphetamine; Dextroamphetamine: (Major) Inhalational general anesthetics may sensitize the myocardium to the effects of dextroamphetamine. Dosages of the amphetamines should be substantially reduced prior to surgery, and caution should be observed with concurrent use of anesthetics.
    Angiotensin II receptor antagonists: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Angiotensin-converting enzyme inhibitors: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Apomorphine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and CNS depressants could result in additive depressant effects.
    Apraclonidine: (Minor) No specific drug interactions were identified with systemic agents and apraclonidine during clinical trials. Theoretically, apraclonidine might potentiate the effects of CNS depressant drugs such as general anesthetics.
    Articaine; Epinephrine: (Major) General anesthetics are known to increase cardiac irritability via myocardial sensitization to catecholamines. These anesthetics can produce ventricular arrhythmias and/or hypertension when used concomitantly with epinephrine.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Major) Concomitant use of codeine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. (Moderate) Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
    Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) General anesthetics potentiate the effects of other CNS depressants, including skeletal muscle relaxants.
    Aspirin, ASA; Carisoprodol: (Moderate) General anesthetics potentiate the effect of other CNS depressants including carisoprodol.
    Aspirin, ASA; Carisoprodol; Codeine: (Major) Concomitant use of codeine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. (Moderate) General anesthetics potentiate the effect of other CNS depressants including carisoprodol.
    Aspirin, ASA; Oxycodone: (Major) Concomitant use of oxycodone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Azelastine: (Minor) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including general anesthetics.
    Azelastine; Fluticasone: (Minor) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including general anesthetics.
    Bacitracin: (Moderate) General anesthetics should be used cautiously in patients receiving systemic bacitracin. Systemic bacitracin may act synergistcally to increase or prolong skeletal muscle relaxation produced by neuromuscular blocking agents and/or general anesthetics. If bacitracin is administered parenterally during surgery, there may be increased skeletal muscle relaxation, and postoperative use may reinstate neuromuscular blockade.
    Baclofen: (Moderate) Concomitant use of skeletal muscle relaxants with other CNS depressants like general anesthetics can result in additive CNS depression.
    Barbiturates: (Moderate) Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
    Belladonna; Opium: (Major) Concomitant use of opium with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Benzhydrocodone; Acetaminophen: (Major) Concomitant use of benzhydrocodone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Benzodiazepines: (Moderate) Concomitant administration can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent.
    Benzphetamine: (Major) Inhalational general anesthetics may sensitize the myocardium to the effects of sympathomimetics. Dosages of sympathomimetics should be substantially reduced prior to surgery, and caution should be observed with concurrent use of anesthetics.
    Beta-adrenergic blockers: (Major) General anesthetics can potentiate the antihypertensive effects of beta-blockers and can produce prolonged hypotension. Beta-blockers may be continued during general anesthesia as long as the patient is monitored for cardiac depressant and hypotensive effects.
    Brompheniramine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Brompheniramine; Carbetapentane; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants inlcuding general anesthetics. (Moderate) Initially, vasopressors may reduce propofol serum concentrations due to increased metabolic clearance secondary to increased hepatic blood flow. An increase in the propofol dose may be required. Additionally, the vasopressor dose may need to be increased over time due to tachyphylaxis. Thus, these drugs may drive each other in a progressively myocardial depressive loop, which could lead to cardiac arrhythmias or cardiac failure. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Brompheniramine; Dextromethorphan; Guaifenesin: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Initially, vasopressors may reduce propofol serum concentrations due to increased metabolic clearance secondary to increased hepatic blood flow. An increase in the propofol dose may be required. Additionally, the vasopressor dose may need to be increased over time due to tachyphylaxis. Thus, these drugs may drive each other in a progressively myocardial depressive loop, which could lead to cardiac arrhythmias or cardiac failure. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Brompheniramine; Phenylephrine: (Moderate) Initially, vasopressors may reduce propofol serum concentrations due to increased metabolic clearance secondary to increased hepatic blood flow. An increase in the propofol dose may be required. Additionally, the vasopressor dose may need to be increased over time due to tachyphylaxis. Thus, these drugs may drive each other in a progressively myocardial depressive loop, which could lead to cardiac arrhythmias or cardiac failure. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Brompheniramine; Pseudoephedrine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Brompheniramine; Pseudoephedrine; Dextromethorphan: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Bupivacaine Liposomal: (Major) If epinephrine is added to bupivacaine, do not use the mixture in a patient during or following treatment with general anesthetics. Concurrent use has been associated with the development of cardiac arrhythmias, and should be avoided, if possible.
    Bupivacaine: (Major) If epinephrine is added to bupivacaine, do not use the mixture in a patient during or following treatment with general anesthetics. Concurrent use has been associated with the development of cardiac arrhythmias, and should be avoided, if possible.
    Bupivacaine; Epinephrine: (Major) General anesthetics are known to increase cardiac irritability via myocardial sensitization to catecholamines. These anesthetics can produce ventricular arrhythmias and/or hypertension when used concomitantly with epinephrine. (Major) If epinephrine is added to bupivacaine, do not use the mixture in a patient during or following treatment with general anesthetics. Concurrent use has been associated with the development of cardiac arrhythmias, and should be avoided, if possible.
    Bupivacaine; Lidocaine: (Major) If epinephrine is added to bupivacaine, do not use the mixture in a patient during or following treatment with general anesthetics. Concurrent use has been associated with the development of cardiac arrhythmias, and should be avoided, if possible. (Moderate) Concomitant use of systemic lidocaine and propofol may increase lidocaine plasma concentrations by reducing lidocaine clearance. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 substrate and propofol is a CYP3A4 inhibitor.
    Bupivacaine; Meloxicam: (Major) If epinephrine is added to bupivacaine, do not use the mixture in a patient during or following treatment with general anesthetics. Concurrent use has been associated with the development of cardiac arrhythmias, and should be avoided, if possible.
    Buspirone: (Moderate) General anesthetics potentiate the effects of CNS depressants.
    Butabarbital: (Moderate) Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
    Butalbital; Acetaminophen: (Moderate) Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
    Butalbital; Acetaminophen; Caffeine: (Moderate) Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Concomitant use of codeine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. (Moderate) Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
    Butorphanol: (Moderate) Concomitant use of butorphanol with other CNS depressants can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
    Calcium, Magnesium, Potassium, Sodium Oxybates: (Major) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with general anesthetics.
    Calcium-channel blockers: (Major) The depression of cardiac contractility, conductivity, and automaticity as well as the vascular dilation associated with general anesthetics may be potentiated by calcium-channel blockers. Alternatively, general anesthetics can potentiate the hypotensive effects of calcium-channel blockers. When used concomitantly, anesthetics and calcium-channel blockers should be titrated carefully to avoid excessive cardiovascular depression.
    Cannabidiol: (Moderate) Consider a dose reduction of propofol as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased propofol exposure is possible. Additive somnolence and sedation may occur. Propofol is a UGT1A9 substrate. In vitro data predicts inhibition of UGT1A9 by cannabidiol potentially resulting in clinically significant interactions.
    Capreomycin: (Moderate) Partial neuromuscular blockade has been reported with capreomycin after the administration of large intravenous doses or rapid intravenous infusion. General anesthetics could potentiate the neuromuscular blocking effect of capreomycin by transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects.
    Capsaicin; Metaxalone: (Moderate) General anesthetics potentiate the effects of other CNS depressants, including skeletal muscle relaxants.
    Carbetapentane; Chlorpheniramine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants inlcuding general anesthetics. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants inlcuding general anesthetics. (Moderate) Initially, vasopressors may reduce propofol serum concentrations due to increased metabolic clearance secondary to increased hepatic blood flow. An increase in the propofol dose may be required. Additionally, the vasopressor dose may need to be increased over time due to tachyphylaxis. Thus, these drugs may drive each other in a progressively myocardial depressive loop, which could lead to cardiac arrhythmias or cardiac failure. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants inlcuding general anesthetics. (Moderate) Initially, vasopressors may reduce propofol serum concentrations due to increased metabolic clearance secondary to increased hepatic blood flow. An increase in the propofol dose may be required. Additionally, the vasopressor dose may need to be increased over time due to tachyphylaxis. Thus, these drugs may drive each other in a progressively myocardial depressive loop, which could lead to cardiac arrhythmias or cardiac failure. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Carbetapentane; Guaifenesin: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants inlcuding general anesthetics.
    Carbetapentane; Guaifenesin; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants inlcuding general anesthetics. (Moderate) Initially, vasopressors may reduce propofol serum concentrations due to increased metabolic clearance secondary to increased hepatic blood flow. An increase in the propofol dose may be required. Additionally, the vasopressor dose may need to be increased over time due to tachyphylaxis. Thus, these drugs may drive each other in a progressively myocardial depressive loop, which could lead to cardiac arrhythmias or cardiac failure.
    Carbetapentane; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants inlcuding general anesthetics. (Moderate) Initially, vasopressors may reduce propofol serum concentrations due to increased metabolic clearance secondary to increased hepatic blood flow. An increase in the propofol dose may be required. Additionally, the vasopressor dose may need to be increased over time due to tachyphylaxis. Thus, these drugs may drive each other in a progressively myocardial depressive loop, which could lead to cardiac arrhythmias or cardiac failure.
    Carbetapentane; Phenylephrine; Pyrilamine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants inlcuding general anesthetics. (Moderate) Initially, vasopressors may reduce propofol serum concentrations due to increased metabolic clearance secondary to increased hepatic blood flow. An increase in the propofol dose may be required. Additionally, the vasopressor dose may need to be increased over time due to tachyphylaxis. Thus, these drugs may drive each other in a progressively myocardial depressive loop, which could lead to cardiac arrhythmias or cardiac failure. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Carbetapentane; Pseudoephedrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants inlcuding general anesthetics.
    Carbetapentane; Pyrilamine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants inlcuding general anesthetics. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Carbidopa; Levodopa: (Major) If administered before halogenated anesthetics, levodopa without concomitant use of a decarboxylase inhibitor has been associated with cardiac arrhythmias. This interaction is presumably due to the levodopa-induced increases in plasma dopamine. Levodopa single-agent therapy should be discontinued 6 to 8 hours before administering halogenated anesthetics. Otherwise, when general anesthetics are required, levodopa may be continued as long as the patient is permitted to take oral medication. Patients should be observed for signs of neuroleptic malignant syndrome while therapy is interrupted, and the usual levodopa regimen should be administered as soon as the patient is able to take oral medication.
    Carbidopa; Levodopa; Entacapone: (Major) If administered before halogenated anesthetics, levodopa without concomitant use of a decarboxylase inhibitor has been associated with cardiac arrhythmias. This interaction is presumably due to the levodopa-induced increases in plasma dopamine. Levodopa single-agent therapy should be discontinued 6 to 8 hours before administering halogenated anesthetics. Otherwise, when general anesthetics are required, levodopa may be continued as long as the patient is permitted to take oral medication. Patients should be observed for signs of neuroleptic malignant syndrome while therapy is interrupted, and the usual levodopa regimen should be administered as soon as the patient is able to take oral medication.
    Carbinoxamine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Carbinoxamine; Phenylephrine: (Moderate) Initially, vasopressors may reduce propofol serum concentrations due to increased metabolic clearance secondary to increased hepatic blood flow. An increase in the propofol dose may be required. Additionally, the vasopressor dose may need to be increased over time due to tachyphylaxis. Thus, these drugs may drive each other in a progressively myocardial depressive loop, which could lead to cardiac arrhythmias or cardiac failure. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Carbinoxamine; Pseudoephedrine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Carisoprodol: (Moderate) General anesthetics potentiate the effect of other CNS depressants including carisoprodol.
    Celecoxib; Tramadol: (Major) Concomitant use of tramadol with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Cenobamate: (Moderate) Although CNS depression is a desired effect of general anesthetics, monitor patients also receiving cenobamate closely for additive CNS depression that may prolong recovery after administration of a general anesthetic.
    Central-acting adrenergic agents: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents. Reduced dosages of antihypertensives may be required during heavy sedation.
    Cetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with general anesthetics should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. CNS depression is a desired effect of general anesthetics; however, concurrent use with a CNS depressant may prolong recovery. If concurrent use is necessary, monitor patients closely.
    Cetirizine; Pseudoephedrine: (Moderate) Concurrent use of cetirizine/levocetirizine with general anesthetics should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. CNS depression is a desired effect of general anesthetics; however, concurrent use with a CNS depressant may prolong recovery. If concurrent use is necessary, monitor patients closely.
    Chlophedianol; Dexbrompheniramine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Chlophedianol; Guaifenesin; Phenylephrine: (Moderate) Initially, vasopressors may reduce propofol serum concentrations due to increased metabolic clearance secondary to increased hepatic blood flow. An increase in the propofol dose may be required. Additionally, the vasopressor dose may need to be increased over time due to tachyphylaxis. Thus, these drugs may drive each other in a progressively myocardial depressive loop, which could lead to cardiac arrhythmias or cardiac failure.
    Chlorcyclizine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Chlordiazepoxide; Amitriptyline: (Moderate) General anesthetics like propofol may produce additive CNS depression when used in patients taking tricyclic antidepressants.
    Chloroprocaine: (Major) Due to the cardiotoxic potential of all local anesthetics, they should be used with caution with other agents that can prolong the QT interval, such as general anesthetics. If epinephrine is added to chloroprocaine, do not use the mixture in a patient during or following treatment with general anesthetics.
    Chlorpheniramine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Chlorpheniramine; Codeine: (Major) Concomitant use of codeine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Chlorpheniramine; Dextromethorphan: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Initially, vasopressors may reduce propofol serum concentrations due to increased metabolic clearance secondary to increased hepatic blood flow. An increase in the propofol dose may be required. Additionally, the vasopressor dose may need to be increased over time due to tachyphylaxis. Thus, these drugs may drive each other in a progressively myocardial depressive loop, which could lead to cardiac arrhythmias or cardiac failure. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Major) Concomitant use of dihydrocodeine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. (Moderate) Initially, vasopressors may reduce propofol serum concentrations due to increased metabolic clearance secondary to increased hepatic blood flow. An increase in the propofol dose may be required. Additionally, the vasopressor dose may need to be increased over time due to tachyphylaxis. Thus, these drugs may drive each other in a progressively myocardial depressive loop, which could lead to cardiac arrhythmias or cardiac failure. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Chlorpheniramine; Hydrocodone: (Major) Concomitant use of hydrocodone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Chlorpheniramine; Phenylephrine: (Moderate) Initially, vasopressors may reduce propofol serum concentrations due to increased metabolic clearance secondary to increased hepatic blood flow. An increase in the propofol dose may be required. Additionally, the vasopressor dose may need to be increased over time due to tachyphylaxis. Thus, these drugs may drive each other in a progressively myocardial depressive loop, which could lead to cardiac arrhythmias or cardiac failure. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Chlorpheniramine; Pseudoephedrine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Chlorzoxazone: (Moderate) General anesthetics potentiate the effects of other CNS depressants, including skeletal muscle relaxants.
    Cholinesterase inhibitors: (Moderate) Muscle relaxation produced by succinylcholine can be prolonged when the drug is administered with a cholinesterase inhibitor. If used during surgery, extended respiratory depression could result from prolonged neuromuscular blockade. Other neuromuscular blockers may interact with cholinesterase inhibitors in a similar fashion. Cholinesterase inhibitors are therefore also likely to exaggerate muscle relaxation under general anesthetics.
    Clemastine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Clobazam: (Moderate) Clobazam, a benzodiazepine, may cause drowsiness or other CNS effects. Potentiation of CNS effects (i.e., increased sedation or respiratory depression) may occur when clobazam is combined with other CNS depressants such as general anesthetics.
    Clomipramine: (Moderate) General anesthetics like propofol may produce additive CNS depression when used in patients taking tricyclic antidepressants.
    Clozapine: (Moderate) Clozapine can potentiate the actions of other CNS depressants such as the general anesthetics. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
    Codeine: (Major) Concomitant use of codeine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Codeine; Guaifenesin: (Major) Concomitant use of codeine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Codeine; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of codeine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of codeine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. (Moderate) Initially, vasopressors may reduce propofol serum concentrations due to increased metabolic clearance secondary to increased hepatic blood flow. An increase in the propofol dose may be required. Additionally, the vasopressor dose may need to be increased over time due to tachyphylaxis. Thus, these drugs may drive each other in a progressively myocardial depressive loop, which could lead to cardiac arrhythmias or cardiac failure.
    Codeine; Promethazine: (Major) Concomitant use of codeine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Colistin: (Moderate) General anesthetics can potentiate the neuromuscular blocking effect of colistimethate sodium by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
    COMT inhibitors: (Major) Additive CNS depression and hypotension may occur when general anesthetics and COMT inhibitors are used together. Monitor patients closely for additive effects that may prolong recovery.
    Cyclizine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Cyproheptadine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Dantrolene: (Moderate) General anesthetics potentiate the effects of other CNS depressants, including skeletal muscle relaxants.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Use caution if ritonavir is coadministered with propofol due to the potential for decreased propofol exposure which may decrease its efficacy. Propofol is a CYP2B6 substrate and ritonavir is a CYP2B6 inducer.
    Desipramine: (Moderate) General anesthetics like propofol may produce additive CNS depression when used in patients taking tricyclic antidepressants.
    Dexbrompheniramine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Dexbrompheniramine; Pseudoephedrine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Dexchlorpheniramine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Dexmedetomidine: (Moderate) Coadministration of dexmedetomidine with general anesthetics is likely to lead to an enhancement of anesthetic, sedative, or cardiovascular effects. Due to possible pharmacodynamic interactions, when co-administered with dexmedetomidine, a reduction in dosage of dexmedetomidine or the concomitant anesthetic may be required. Specific studies have confirmed these pharmacodynamic effects with sevoflurane, isoflurane, and propofol. No pharmacokinetic interactions between dexmedetomidine and isoflurane or propofol have been demonstrated.
    Dextroamphetamine: (Major) Inhalational general anesthetics may sensitize the myocardium to the effects of dextroamphetamine. Dosages of the amphetamines should be substantially reduced prior to surgery, and caution should be observed with concurrent use of anesthetics.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Initially, vasopressors may reduce propofol serum concentrations due to increased metabolic clearance secondary to increased hepatic blood flow. An increase in the propofol dose may be required. Additionally, the vasopressor dose may need to be increased over time due to tachyphylaxis. Thus, these drugs may drive each other in a progressively myocardial depressive loop, which could lead to cardiac arrhythmias or cardiac failure. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Initially, vasopressors may reduce propofol serum concentrations due to increased metabolic clearance secondary to increased hepatic blood flow. An increase in the propofol dose may be required. Additionally, the vasopressor dose may need to be increased over time due to tachyphylaxis. Thus, these drugs may drive each other in a progressively myocardial depressive loop, which could lead to cardiac arrhythmias or cardiac failure.
    Dichlorphenamide: (Moderate) Use dichlorphenamide and propofol together with caution as both drugs can cause metabolic acidosis. Concurrent use may increase the severity of metabolic acidosis. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
    Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
    Dimenhydrinate: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Diphenhydramine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Diphenhydramine; Ibuprofen: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Diphenhydramine; Naproxen: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Diphenhydramine; Phenylephrine: (Moderate) Initially, vasopressors may reduce propofol serum concentrations due to increased metabolic clearance secondary to increased hepatic blood flow. An increase in the propofol dose may be required. Additionally, the vasopressor dose may need to be increased over time due to tachyphylaxis. Thus, these drugs may drive each other in a progressively myocardial depressive loop, which could lead to cardiac arrhythmias or cardiac failure. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Dopamine: (Moderate) Initially, vasopressors may reduce propofol serum concentrations due to increased metabolic clearance secondary to increased hepatic blood flow. An increase in the propofol dose may be required. Additionally, the vasopressor dose may need to be increased over time due to tachyphylaxis. Thus, these drugs may drive each other in a progressively myocardial depressive loop, which could lead to cardiac arrhythmias or cardiac failure.
    Doxazosin: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Doxepin: (Moderate) General anesthetics like propofol may produce additive CNS depression when used in patients taking tricyclic antidepressants.
    Doxylamine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Doxylamine; Pyridoxine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Dronabinol: (Moderate) Concomitant use of dronabinol with other CNS depressants like general anesthetics can potentiate the effects of dronabinol on respiratory depression.
    Droperidol: (Major) Central nervous system (CNS) depressants (e.g., general anesthetics) have additive or potentiating effects with droperidol. Following administration of droperidol, the dose of the other CNS depressant should be reduced.
    Dyphylline: (Moderate) Methylxanthines and inhaled general anesthetics have been associated with adverse cardiovascular effects. Concurrent use may increase the risk of such effects including cardiac arrhythmias.
    Dyphylline; Guaifenesin: (Moderate) Methylxanthines and inhaled general anesthetics have been associated with adverse cardiovascular effects. Concurrent use may increase the risk of such effects including cardiac arrhythmias.
    Ephedrine: (Moderate) Carefully monitor blood pressure in patients who have received both ephedrine and propofol; propofol augments the pressor effect of ephedrine.
    Ephedrine; Guaifenesin: (Moderate) Carefully monitor blood pressure in patients who have received both ephedrine and propofol; propofol augments the pressor effect of ephedrine.
    Epinephrine: (Major) General anesthetics are known to increase cardiac irritability via myocardial sensitization to catecholamines. These anesthetics can produce ventricular arrhythmias and/or hypertension when used concomitantly with epinephrine.
    Eplerenone: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Epoprostenol: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Esketamine: (Major) Although CNS depression is a desired effect of general anesthetics, patients also receiving esketamine should be closely monitored for additive effects that may prolong recovery after administration of a general anesthetic. If possible, avoid scheduling a treatment session with esketamine on the same day that general anesthesia is required. Patients who have received a dose of esketamine should be instructed not to drive or engage in other activities requiring complete mental alertness until the next day after a restful sleep.
    Eszopiclone: (Moderate) A temporary dose reduction of eszopiclone should be considered following administration of general anesthetics. The risk of next-day psychomotor impairment is increased during co-administration of eszopiclone and other CNS depressants, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
    Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
    Etomidate: (Minor) Propofol potentiates CNS depression and may enhance the sedative, respiratory depressive, and hypotensive effects of other general anesthetics. A reduced dose of propofol may be needed for induction if it is used in conjunction with other medications that cause CNS depression. The use of isoflurane, enflurane, or halothane with propofol has not been extensively evaluated.
    Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and general anesthetics. Concurrent use may result in additive CNS depression.
    Fentanyl: (Major) Concomitant use of fentanyl with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
    Gabapentin: (Major) Concomitant use of general anesthetics with gabapentin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of excessive respiratory depression. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Gentamicin: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving gentamicin.
    Guaifenesin; Hydrocodone: (Major) Concomitant use of hydrocodone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of hydrocodone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Guaifenesin; Phenylephrine: (Moderate) Initially, vasopressors may reduce propofol serum concentrations due to increased metabolic clearance secondary to increased hepatic blood flow. An increase in the propofol dose may be required. Additionally, the vasopressor dose may need to be increased over time due to tachyphylaxis. Thus, these drugs may drive each other in a progressively myocardial depressive loop, which could lead to cardiac arrhythmias or cardiac failure.
    Haloperidol: (Major) Haloperidol can potentiate the actions of other CNS depressants such as general anesthetics. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
    Homatropine; Hydrocodone: (Major) Concomitant use of hydrocodone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Hydrocodone: (Major) Concomitant use of hydrocodone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Hydrocodone; Ibuprofen: (Major) Concomitant use of hydrocodone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Hydrocodone; Pseudoephedrine: (Major) Concomitant use of hydrocodone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Hydromorphone: (Major) Concomitant use of hydromorphone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Hydroxyzine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Ibuprofen; Oxycodone: (Major) Concomitant use of oxycodone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Iloprost: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Imipramine: (Moderate) General anesthetics like propofol may produce additive CNS depression when used in patients taking tricyclic antidepressants.
    Ionic Contrast Media: (Moderate) General anesthesia may be indicated in the performance of some procedures in young or uncooperative children and in selected adult patients; however, a higher incidence of adverse reactions has been reported to ionic contrast media in these patients. This may be attributable to the inability of the patient to identify untoward symptoms, or to the hypotensive effect of anesthesia, which can prolong the circulation time and increase the duration of contact of the contrast agent.
    Isoproterenol: (Major) Both isoproterenol and general anesthetics sensitize myocardial tissue to the development of potentially life-threatening cardiac arrhythmias. Concomitant use of isoproterenol with general anesthetics can increase the risk of developing this adverse reaction.
    Kanamycin: (Moderate) General anesthetics may be associated with enhanced neuromuscular blocking effects. Many pharmacy references mention neuromuscular blockade as an adverse reaction of aminoglycoside antibiotics, however, it appears this is only seen when aminoglycosides are used to irrigate the abdominal cavity during surgery, a practice which has been discouraged. It is believed that this effect is less likely to occur with parenteral aminoglycoside therapy since patients are exposed to smaller amounts of drug. Nevertheless, patients receiving general anesthetics should be observed for exaggerated effects if they are receiving aminoglycosides.
    Lasmiditan: (Moderate) Although CNS depression is a desired effect of general anesthetics, patients also receiving lasmiditan should be closely monitored for additive effects that may prolong recovery after administration of a general anesthetic.
    Lemborexant: (Moderate) Although CNS depression is a desired effect of general anesthetics, monitor patients also receiving lemborexant closely for additive CNS depression that may prolong recovery after administration of a general anesthetic.
    Levocetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with general anesthetics should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. CNS depression is a desired effect of general anesthetics; however, concurrent use with a CNS depressant may prolong recovery. If concurrent use is necessary, monitor patients closely.
    Levodopa: (Major) If administered before halogenated anesthetics, levodopa without concomitant use of a decarboxylase inhibitor has been associated with cardiac arrhythmias. This interaction is presumably due to the levodopa-induced increases in plasma dopamine. Levodopa single-agent therapy should be discontinued 6 to 8 hours before administering halogenated anesthetics. Otherwise, when general anesthetics are required, levodopa may be continued as long as the patient is permitted to take oral medication. Patients should be observed for signs of neuroleptic malignant syndrome while therapy is interrupted, and the usual levodopa regimen should be administered as soon as the patient is able to take oral medication.
    Levorphanol: (Major) Concomitant use of levorphanol with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Reduce the initial dose of levorphanol by approximately 50% or more. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Lidocaine: (Moderate) Concomitant use of systemic lidocaine and propofol may increase lidocaine plasma concentrations by reducing lidocaine clearance. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 substrate and propofol is a CYP3A4 inhibitor.
    Lidocaine; Epinephrine: (Major) General anesthetics are known to increase cardiac irritability via myocardial sensitization to catecholamines. These anesthetics can produce ventricular arrhythmias and/or hypertension when used concomitantly with epinephrine. (Moderate) Concomitant use of systemic lidocaine and propofol may increase lidocaine plasma concentrations by reducing lidocaine clearance. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 substrate and propofol is a CYP3A4 inhibitor.
    Lidocaine; Prilocaine: (Major) Local anesthetics may result in QT prolongation and should be used with caution with other agents that can prolong the QT interval including halogenated anesthetics (i.e., desflurane, enflurane, halothane, isoflurane, and sevoflurane). Also, If epinephrine is added to prilocaine, do not use the mixture in a patient during or following treatment with general anesthetics. Concurrent use has been associated with the development of cardiac arrhythmias, and should be avoided, if possible. (Moderate) Concomitant use of systemic lidocaine and propofol may increase lidocaine plasma concentrations by reducing lidocaine clearance. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 substrate and propofol is a CYP3A4 inhibitor.
    Lisdexamfetamine: (Moderate) Closely monitor vital signs when general anesthetics and lisdexamfetamine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Lisdexamfetamine may enhance the sympathomimetic effects of general anesthetics.
    Lofexidine: (Moderate) Monitor for excessive hypotension and sedation during coadministration of lofexidine and propofol. Lofexidine can potentiate the effects of CNS depressants.
    Loop diuretics: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Lopinavir; Ritonavir: (Moderate) Use caution if ritonavir is coadministered with propofol due to the potential for decreased propofol exposure which may decrease its efficacy. Propofol is a CYP2B6 substrate and ritonavir is a CYP2B6 inducer.
    Loxapine: (Moderate) Loxapine can potentiate the actions of other CNS depressants such as general anesthetics. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
    Lumateperone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lumateperone and general anesthetics. Concurrent use may result in additive CNS depression. Monitor patients closely for additive effects that may prolong recovery after use of a general anesthetic.
    Maprotiline: (Moderate) General anesthetics may produce additive CNS depression when used in patients taking maprotiline.
    Mecamylamine: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Meclizine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Meperidine: (Major) Concomitant use of meperidine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Meperidine; Promethazine: (Major) Concomitant use of meperidine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Meprobamate: (Moderate) The effects of CNS depressant drugs, such as meprobamate, may increase when administered concurrently with general anesthetics. A temporary dose reduction of meprobamate should be considered following administration of general anesthetics. The risk of next-day psychomotor impairment is increased during co-administration, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
    Metaxalone: (Moderate) General anesthetics potentiate the effects of other CNS depressants, including skeletal muscle relaxants.
    Methadone: (Moderate) Concomitant use of methadone with another CNS depressant can lead to additive respiratory depression, hypotension, profound sedation, or coma; examples include general anesthetics. Prior to concurrent use of methadone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Methadone should be used with caution and in reduced dosages if used concurrently with a CNS depressant; in opioid-naive adults, use an initial methadone dose of 2.5 mg every 12 hours. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression.
    Methamphetamine: (Moderate) Closely monitor vital signs when general anesthetics and methamphetamine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Methamphetamine may enhance the sympathomimetic effects of general anesthetics.
    Methohexital: (Moderate) Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
    Midodrine: (Moderate) Initially, vasopressors may reduce propofol serum concentrations due to increased metabolic clearance secondary to increased hepatic blood flow. An increase in the propofol dose may be required. Additionally, the vasopressor dose may need to be increased over time due to tachyphylaxis. Thus, these drugs may drive each other in a progressively myocardial depressive loop, which could lead to cardiac arrhythmias or cardiac failure.
    Minocycline: (Moderate) Injectable minocycline contains magnesium sulfate heptahydrate. Because of the CNS-depressant effects of magnesium sulfate, additive central-depressant effects can occur following concurrent administration with CNS depressants such as general anesthetics. Caution should be exercised when using these agents concurrently. Additionally, the concurrent use of tetracycline and methoxyflurane has been reported to result in fatal renal toxicity. Use caution when administering other tetracyclines.
    Mirtazapine: (Moderate) Consistent with the pharmacology of mirtazapine and the CNS depression that may occur, additive effects may occur with other CNS depressants, including propofol. Close monitoring is recommended in patients receiving mirtazapine and requiring an anesthetic.
    Monoamine oxidase inhibitors: (Major) Discontinue monoamine oxidase inhibitors (MAOIs) at least 10 days prior to elective surgery requiring use of general anesthetics due to the potential for significant hypotension. If this is not possible, carefully consider the risk of agents and techniques (e.g., epidural or spinal anesthesia) that increase the risk for hypotension.
    Morphine: (Major) Concomitant use of morphine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Morphine; Naltrexone: (Major) Concomitant use of morphine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Nabilone: (Major) Concomitant use of nabilone with other CNS depressants like general anesthetics can potentiate the effects of nabilone on the central nervous system. Additive drowsiness and CNS depression can occur.
    Nalbuphine: (Moderate) Concomitant use of nalbuphine with other CNS depressants can potentiate the effects of nalbuphine on respiratory depression, CNS depression, and sedation.
    Nesiritide, BNP: (Major) The potential for hypotension may be increased when coadministering nesiritide with other hypotensive drugs, including general anesthetics.
    Nirmatrelvir; Ritonavir: (Moderate) Use caution if ritonavir is coadministered with propofol due to the potential for decreased propofol exposure which may decrease its efficacy. Propofol is a CYP2B6 substrate and ritonavir is a CYP2B6 inducer.
    Norepinephrine: (Moderate) Norepinephrine interacts with general anesthetics because the anesthetics increase cardiac irritability, which can lead to arrhythmias.
    Nortriptyline: (Moderate) General anesthetics like propofol may produce additive CNS depression when used in patients taking tricyclic antidepressants.
    Oliceridine: (Major) Concomitant use of oliceridine with general anesthetics may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with general anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
    Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Use caution if ritonavir is coadministered with propofol due to the potential for decreased propofol exposure which may decrease its efficacy. Propofol is a CYP2B6 substrate and ritonavir is a CYP2B6 inducer.
    Orphenadrine: (Moderate) General anesthetics potentiate the effects of other CNS depressants, including skeletal muscle relaxants.
    Oxycodone: (Major) Concomitant use of oxycodone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Oxymorphone: (Major) Concomitant use of oxymorphone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Reduce the initial oxymorphone dosage by 1/3 to 1/2. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Oxytocin: (Major) Adverse cardiovascular effects can develop as a result of concomitant administration of oxytocin with general anesthetics, especially in those with preexisting valvular heart disease. Cyclopropane, when administered with or without oxytocin, has been implicated in producing maternal sinus bradycardia, abnormal atrioventricular rhythms, hypotension, and increases in heart rate, cardiac output, and systemic venous return. In addition, halogenated anesthetics decrease uterine responsiveness to oxytocics (e.g., oxytocin) and, in high doses, can abolish it, increasing the risk of uterine hemorrhage. Halothane is a potent uterine relaxant. Enflurane displaces the myometrial response curve to oxytocin so that at lower concentrations of enflurane oxytocin will restore uterine contractions. However, as the dose of enflurane progresses (somewhere between 1.5 to 3% delivered enflurane) the response to oxytocin is inhibited. It is not clear if other halogenated anesthetics would interact with oxytocics in this manner.
    Papaverine: (Moderate) Papaverine is a benzylisoquinoline alkaloid of opium and may have synergistic effects with potent CNS depressants such as general anesthetics, which could lead to enhanced sedation.
    Pentobarbital: (Moderate) Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
    Perphenazine; Amitriptyline: (Moderate) General anesthetics like propofol may produce additive CNS depression when used in patients taking tricyclic antidepressants.
    Phenobarbital: (Moderate) Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
    Phenoxybenzamine: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Phenylephrine: (Moderate) Initially, vasopressors may reduce propofol serum concentrations due to increased metabolic clearance secondary to increased hepatic blood flow. An increase in the propofol dose may be required. Additionally, the vasopressor dose may need to be increased over time due to tachyphylaxis. Thus, these drugs may drive each other in a progressively myocardial depressive loop, which could lead to cardiac arrhythmias or cardiac failure.
    Polymyxin B: (Moderate) Systemic polymyxin B can increase the neuromuscular blockade effects of neuromuscular blockers, general anesthetics, and skeletal muscle relaxants. Polymyxin B affects both pre- and post-synaptic myoneural areas by inhibiting release of acetylcholine pre-synaptically and/or blocking acetylcholine activity post-synaptically. Thus, polymyxin B acts synergistically with these agents.
    Potassium-sparing diuretics: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Prazosin: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Pregabalin: (Major) Concomitant use of general anesthetics with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of excessive respiratory depression. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Prilocaine: (Major) Local anesthetics may result in QT prolongation and should be used with caution with other agents that can prolong the QT interval including halogenated anesthetics (i.e., desflurane, enflurane, halothane, isoflurane, and sevoflurane). Also, If epinephrine is added to prilocaine, do not use the mixture in a patient during or following treatment with general anesthetics. Concurrent use has been associated with the development of cardiac arrhythmias, and should be avoided, if possible.
    Prilocaine; Epinephrine: (Major) General anesthetics are known to increase cardiac irritability via myocardial sensitization to catecholamines. These anesthetics can produce ventricular arrhythmias and/or hypertension when used concomitantly with epinephrine. (Major) Local anesthetics may result in QT prolongation and should be used with caution with other agents that can prolong the QT interval including halogenated anesthetics (i.e., desflurane, enflurane, halothane, isoflurane, and sevoflurane). Also, If epinephrine is added to prilocaine, do not use the mixture in a patient during or following treatment with general anesthetics. Concurrent use has been associated with the development of cardiac arrhythmias, and should be avoided, if possible.
    Primidone: (Moderate) Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
    Procaine: (Major) Local anesthetics may result in QT prolongation and should be used with caution with other agents that can prolong the QT interval including halogenated anesthetics (i.e., desflurane, enflurane, halothane, isoflurane, and sevoflurane). Also, If epinephrine is added to procaine, do not use the mixture in a patient during or following treatment with general anesthetics. Concurrent use has been associated with the development of cardiac arrhythmias, and should be avoided, if possible.
    Procarbazine: (Major) Patients receiving drugs that possess MAOI properties, such as procarbazine, may have an increased risk of hypotension after administration of general anesthetics. Procarbazine should be discontinued for at least 10 days prior to elective surgery.
    Promethazine; Phenylephrine: (Moderate) Initially, vasopressors may reduce propofol serum concentrations due to increased metabolic clearance secondary to increased hepatic blood flow. An increase in the propofol dose may be required. Additionally, the vasopressor dose may need to be increased over time due to tachyphylaxis. Thus, these drugs may drive each other in a progressively myocardial depressive loop, which could lead to cardiac arrhythmias or cardiac failure.
    Protriptyline: (Moderate) General anesthetics like propofol may produce additive CNS depression when used in patients taking tricyclic antidepressants.
    Pseudoephedrine; Triprolidine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Pyrilamine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Rasagiline: (Moderate) Patients receiving drugs that possess MAOI properties, such as rasagiline, may have an increased risk of hypotension after administration of general anesthetics, although specific studies are not available. Combined hypotensive effects are also possible with the combined use of MAOIs and spinal anesthetics.
    Reserpine: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Ritonavir: (Moderate) Use caution if ritonavir is coadministered with propofol due to the potential for decreased propofol exposure which may decrease its efficacy. Propofol is a CYP2B6 substrate and ritonavir is a CYP2B6 inducer.
    Secobarbital: (Moderate) Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
    Sedating H1-blockers: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Selegiline: (Moderate) Although CNS depression is a desired effect of general anesthetics, patients also receiving selegiline should be closely monitored for additive effects that may prolong recovery after administration of general anesthetics.
    Sodium Oxybate: (Major) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with general anesthetics.
    Sotalol: (Major) General anesthetics can potentiate the antihypertensive effects of beta-blockers and can produce prolonged hypotension.
    St. John's Wort, Hypericum perforatum: (Major) St. John's wort, Hypericum perforatum, may intensify or prolong the effects of propofol; profound hypotension has also been reported. In one report, the authors recommend that patients should discontinue taking St. John's Wort at least 5 days prior to anesthesia. The American Society of Anesthesiologists has recommended that patients stop taking herbal medications at least 2 to 3 weeks before surgery to decrease the risk of adverse reactions.
    Streptomycin: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving streptomycin.
    Suvorexant: (Moderate) CNS depressant drugs, including general anesthetics, may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of either suvorexant or the CNS depressant may be needed in some cases.
    Tapentadol: (Major) Concomitant use of tapentadol with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Terazosin: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Tetracaine: (Major) Local anesthetics may result in QT prolongation and should be used with caution with other agents that can prolong the QT interval including halogenated anesthetics (i.e., desflurane, enflurane, halothane, isoflurane, and sevoflurane). Also, If epinephrine is added to tetracaine, do not use the mixture in a patient during or following treatment with general anesthetics. Concurrent use has been associated with the development of cardiac arrhythmias, and should be avoided, if possible.
    Theophylline, Aminophylline: (Moderate) Aminophylline used concurrently with inhaled general anesthetics may increase the risk of cardiac arrhythmias. (Moderate) Theophylline used concurrently with inhaled general anesthetics may increase the risk of cardiac arrhythmias. When ketamine and theophylline are given concurrently a clinically significant reduction in the seizure threshold is observed.
    Thiazide diuretics: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Thiothixene: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as general anesthetics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Tobramycin: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving tobramycin.
    Tramadol: (Major) Concomitant use of tramadol with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Tramadol; Acetaminophen: (Major) Concomitant use of tramadol with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Treprostinil: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Tricyclic antidepressants: (Moderate) General anesthetics like propofol may produce additive CNS depression when used in patients taking tricyclic antidepressants.
    Trimipramine: (Moderate) General anesthetics like propofol may produce additive CNS depression when used in patients taking tricyclic antidepressants.
    Triprolidine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Valproic Acid, Divalproex Sodium: (Major) Concomitant use of valproate and propofol may result in elevated blood concentrations of propofol. If used together, reduce the dose of propofol and monitor patients closely for signs of increased sedation or cardiorespiratory depression.
    Vancomycin: (Moderate) The concurrent administration of vancomycin and anesthetics has been associated with erythema, histamine-like flushing, and anaphylactoid reactions.
    Vasodilators: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Warfarin: (Moderate) The administration of high-dose propofol infusions has been associated with the reversal of warfarin anticoagulation. Propofol is emulsified with soybean oil 10%, which contains vitamin K. Close monitoring of the anticoagulation effect of warfarin is recommended for patients requiring concurrent propofol.
    Zaleplon: (Moderate) Coadministration of zaleplon and general anesthetics may result in additive CNS depressant effects. In premarketing studies, zaleplon potentiated the CNS effects of ethanol, imipramine, and thioridazine for at least 2 to 4 hours. A similar interaction may occur with zaleplon and other CNS depressants including general anesthetics. If concurrent use is necessary, monitor for additive side effects. A temporary dose reduction of zaleplon should be considered following administration of general anesthetics. The risk of next-day psychomotor impairment is increased during co-administration, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
    Zolpidem: (Moderate) The effects of CNS depressant drugs, such as zolpidem, may increase when administered concurrently with general anesthetics. A temporary dose reduction of the CNS depressant should be considered following administration of general anesthetics. For Intermezzo brand of sublingual zolpidem tablets, reduce the dose to 1.75 mg/night.

    PREGNANCY AND LACTATION

    Pregnancy

    Propofol is excreted in human milk. Variable concentrations in human milk have been reported with administration of propofol to breast-feeding mothers in the postpartum period. Adverse reactions in breastfed infants have not been reported. The effects of propofol on human milk production are unknown.[31036] Some experts state that in general, healthy term infants can safely nurse after a surgical procedure, as soon as the mother is awake and alert.[28006] [48668] Propofol is minimally excreted in breast milk, and the oral bioavailability to a nursing infant is likely to be very low. In a study of 5 women (6 to 15 weeks postpartum) given a single dose of propofol 2.5 mg/kg, milk samples collected 5 to 24 hours after injection indicate that an infant would receive approximately 0.0052 mg/kg (or 0.2% of the maternal weight-adjusted dose) in the 24 hours after the dose.[62842] [62843] The effects of oral propofol ingestion by an infant are unknown, but it appears that the risk of infant exposure to the drug is low.[28006]

    MECHANISM OF ACTION

    Mechanism of Action: Propofol appears to inhibit the NMDA subtype of glutamate receptors by channel gating modulation and has agonistic activity at the GABAA receptor. Propofol enhances the amplitude of currents evoked by subthreshold concentrations of gamma-aminobutyric acid (GABA) and directly activates the GABAA receptor in the absence of GABA. Propofol activates chloride channels in the ß1 subunit of GABAA, but it is unknown if propofol binds directly to the receptor, binding sites, or if the effects are a result of mediation of distinct mechanisms, such as second messengers. Propofol and benzodiazepines have similar effects on GABAA receptor deactivation but different effects on desensitization. Receptor desensitization causes a fall from a peak (activation) due to agonist application to an apparent steady state. Deactivation is the rate of decay to baseline following the termination of drug application. Both drugs slow the rate of deactivation, but only propofol decreases the rate and extent of receptor desensitization in the presence of saturating concentrations of GABA. In the presence of sub-maximal concentrations of GABA, both drugs slow the rate and extent of receptor desensitization. The anesthetic and amnesic properties of propofol may be wholely or partly a result of NMDA-mediated excitatory neurotransmission depression. The utility of propofol for refractory migraine, status epilepticus, and delirium tremens may be due to enhanced inhibitory synaptic transmission from GABAA receptor agonism or glutamate receptor inhibition.Propofol with hypocarbia increases cerebrovascular resistance and decreases cerebral blood flow, cerebral metabolic oxygen consumption, and intracranial pressure. The decrease in cerebral blood flow and intraocular pressure is likely a result of a decrease in systemic vascular resistance. Propofol does not affect cerebrovascular reactivity to changes in arterial carbon dioxide tension.Propofol has been shown to possess antiemetic properties. Propofol reduces the concentration of serotonin and 5-hydroxyindoleacetic acid in the area postrema. The reduction may be mediated by the GABAA receptor. Propofol also reduces the synaptic transmission in the olfactory cortex, which suggests a decrease in the release of excitatory amino acids like glutamate and aspartate. Propofol does not affect gastric emptying time or dopamine D2 receptors.

    PHARMACOKINETICS

    Propofol is administered intravenously. Propofol pharmacokinetics follow a 3-compartment linear model, with the compartments representing the plasma, rapidly equilibrating tissues, and slowly equilibrating tissues. After an IV bolus dose, there is rapid equilibration between the plasma and the brain. Plasma concentrations initially decline quickly as a result of distribution and metabolic clearance. Distribution accounts for approximately half of this decline; however, distribution decreases as the body tissues equilibrate with plasma and become saturated. The time to tissue saturation depends on the rate and duration of the infusion. Discontinuation of the recommended doses of propofol after the maintenance of anesthesia for approximately 1 hour, or for sedation in the intensive care unit for 1 day, results in a prompt decrease in propofol concentrations and rapid awakening. Longer infusions (e.g., 10 days) result in accumulation of significant tissue stores of propofol, such that the reduction in circulating propofol is slowed and the time to awakening is increased. Distribution half-life is about 2 to 5 minutes. Propofol has a steady-state volume of distribution (10-day infusion) of about 60 L/kg in healthy adults. Propofol clearance ranges from 23 to 50 mL/kg/minute in adult patients. It is primarily eliminated by hepatic conjugation to inactive metabolites, which are excreted by the kidney. A glucuronide conjugate accounts for about 50% of the administered dose. The clearance of propofol exceeds estimated hepatic blood flow, which suggests extrahepatic routes of metabolism. Elimination of propofol is biphasic; terminal elimination is a consequence of the slow release of the drug from fat stores. Initial half-life is rapid (25 to 56 minutes). Terminal half-life is 184 to 309 minutes after a single bolus injection, 277 to 403 minutes after unspecified continuous infusion, and 1 to 3 days after a 10-day continuous infusion, indicating accumulation of propofol with prolonged use.[31036] [54838] [55078]
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP2B6
    Propofol is a CYP2B6 substrate in vitro.[65225]

    Intravenous Route

    Intravenous administration of propofol induces anesthesia, with minimal excitation, usually within 40 seconds from the start of injection (the time for 1 arm-brain circulation). As with other rapidly acting intravenous anesthetic agents, the half-time of the blood-brain equilibration is approximately 1 to 3 minutes, accounting for the rate of induction of anesthesia. Discontinuation of propofol after the maintenance of anesthesia for approximately 1 hour, or for sedation in the intensive care unit for 1 day, results in a prompt decrease in propofol concentrations and rapid awakening. Longer infusions (e.g., 10 days) result in accumulation of significant tissue stores of propofol, such that the reduction in circulating propofol is slowed and the time to awakening is increased. If higher infusion rates have been maintained for a long time, propofol redistribution from fat and muscle to the plasma can be significant and slow recovery. The large contribution of distribution (about 50%) to the fall of propofol plasma concentrations after brief infusions means that after very long infusions a reduction in the infusion rate is appropriate by as much as half the initial infusion rate in order to maintain a constant plasma concentration. By daily titration of propofol to achieve only the minimum effective therapeutic concentration, rapid awakening within 10 to 15 minutes can occur even after long-term administration.[31036]