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  • CLASSES

    Other General Anesthetics

    DEA CLASS

    Rx

    DESCRIPTION

    Intravenous, nonbarbiturate anesthetic
    Used for induction and maintenance of anesthesia and sedation of mechanically ventilated adult patients in the intensive care unit
    Induces anesthesia as quickly as thiopental with more rapid emergence

    COMMON BRAND NAMES

    Diprivan, Fresenius Propoven

    HOW SUPPLIED

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

    DOSAGE & INDICATIONS

    For general anesthesia induction.
    For cardiac anesthesia.
    Intravenous dosage
    Adults and Adolescents 17 years and older

    0.5 to 1.5 mg/kg IV as a total dose; administer in approximately 20 mg increments every 10 seconds until onset of anesthesia. Rapid boluses should not be used. Administer anticholinergic agents when increases in vagal tone are anticipated. Dosage should be individualized and titrated. Closely monitor cardiorespiratory status.

    For neurosurgical anesthesia.
    Intravenous dosage
    Adults and Adolescents 17 years and older

    1 to 2 mg/kg IV as a total dose; administer in approximately 20 mg increments every 10 seconds until onset of anesthesia. Dosage should be individualized and titrated. Closely monitor cardiorespiratory status. When increased intracranial pressure is suspected, hyperventilation and hypocarbia should accompany propofol administration.

    Intravenous dosage
    Adults and Adolescents 17 to 54 years who are ASA-PS I or II

    2 to 2.5 mg/kg IV as a total dose; administer in approximately 40 mg increments every 10 seconds until onset of anesthesia. Dosage should be individualized and titrated. Closely monitor cardiorespiratory status.

    Geriatric patients, or Adults and Adolescents 17 to 54 years who are debilitated or ASA-PS III or IV

    1 to 1.5 mg/kg IV as a total dose; administer in approximately 20 mg increments every 10 seconds until onset of anesthesia. Rapid boluses should not be used. Dosage should be individualized and titrated. Closely monitor cardiorespiratory status.

    Children and Adolescents 3 to 16 years

    2.5 to 3.5 mg/kg IV as a single dose over 20 to 30 seconds in healthy patients (ASA-PS I or II). Dosage should be individualized and titrated. A lower dose should be used 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. Closely monitor cardiorespiratory status.

    For general anesthesia maintenance.
    For cardiac anesthesia.
    Continuous Intravenous Infusion dosage
    Adults and Adolescents 17 years and older (low dose propofol with primary opioid)

    50 to 100 mcg/kg/minute (3 to 6 mg/kg/hour) IV as a continuous infusion; initiate immediately after the induction dose. Dosage should be individualized and titrated. When an opioid is used as the primary anesthetic agent, propofol maintenance infusion rates should not be less than 50 mcg/kg/minute (3 mg/kg/hour), and care should be taken to ensure amnesia. Closely monitor cardiorespiratory status.

    Adults and Adolescents 17 years and older (primary propofol with secondary opioid)

    100 to 150 mcg/kg/minute (6 to 9 mg/kg/hour) IV as a continuous infusion; initiate immediately after the induction dose. Dosage should be individualized and titrated. When propofol is used as the primary anesthetic agent, maintenance infusion rates should not be less than 100 mcg/kg/minute (6 mg/kg/hour), and should be supplemented with analgesic levels of continuos opioid administration. Closely monitor cardiorespiratory status.

    For neurosurgical anesthesia.
    Continuous Intravenous Infusion dosage
    Adults and Adolescents 17 years and older

    100 to 200 mcg/kg/minute (6 to 12 mg/kg/hour) IV as a continuous infusion; initiate immediately after the induction dose. Dosage should be individualized and titrated. Infusion rates of 50 to 100 mcg/kg/minute (3 to 6 mg/kg/hour) should be achieved to optimize recovery times. Closely monitor cardiorespiratory status.

    Intermittent Intravenous dosage
    Adults and Adolescents 17 to 54 years who are ASA-PS I or II

    20 to 50 mg IV as needed. Clinical response determines amount and frequency of incremental injections; administer when changes in vital signs indicate a response to surgical stimulation or light anesthesia. Closely monitor cardiorespiratory status.

    Continuous Intravenous Infusion dosage
    Adults and Adolescents 17 to 54 years who are ASA-PS I or II

    150 to 200 mcg/kg/minute (9 to 12 mg/kg/hour) IV as a continuous infusion for 10 to 15 minutes; initiate immediately after the induction dose. Decrease infusion by 30% to 50% during the first 30 minutes of maintenance; infusion rates of 100 to 200 mcg/kg/minute (6 to 12 mg/kg/hour) are typical. Dosage should be individualized and titrated. Infusion rates of 50 to 100 mcg/kg/minute (3 to 6 mg/kg/hour) should be achieved to optimize recovery times. Closely monitor cardiorespiratory status.

    Geriatric patients, or Adults and Adolescents 17 to 54 years who are debilitated or ASA-PS III or IV

    50 to 100 mcg/kg/minute (3 to 6 mg/kg/hour) IV as a continuous infusion; initiate immediately after the induction dose. Dosage should be individualized and titrated. Infusion rates of 50 to 100 mcg/kg/minute (3 to 6 mg/kg/hour) should be achieved to optimize recovery times. Closely monitor cardiorespiratory status.

    Infants, Children, and Adolescents 2 months to 16 years

    200 to 300 mcg/kg/minute (12 to 18 mg/kg/hour) IV as a continuous infusion in healthy patients (ASA-PS I or II); initiate immediately after the induction dose. Decrease the infusion rate after 30 minutes if clinical signs of light anesthesia are not present; infusion rates of 125 to 150 mcg/kg/minute (7.5 to 9 mg/kg/hour) are typically required. Dosage should be individualized and titrated. Lower initial infusion rates should be used in patients with severe systemic disease (ASA-PS III or IV). Young pediatric patients may require higher doses compared to older pediatric patients. Closely monitor cardiorespiratory status.

    For intensive care sedation induction and sedation maintenance of mechanically ventilated patients.
    Continuous Intravenous Infusion dosage
    Adults and Adolescents 17 years and older

    5 mcg/kg/minute (0.3 mg/kg/hour) IV as a continuous infusion for at least 5 minutes; increase by 5 to 10 mcg/kg/minute (0.3 to 0.6 mg/kg/hour) increments every 5 to 10 minutes until desired clinical effect is achieved. Reduce dosage in patients with severe systemic disease (ASA-PS III or IV) or who have received large doses of narcotic. Usual maintenance: 5 to 50 mcg/kg/minute (0.3 to 3 mg/kg/hour) IV, however higher doses may be required. Do not exceed 67 mcg/kg/minute (4 mg/kg/hour) IV unless benefits outweigh risks. Bolus administration of propofol 10 to 20 mg/dose IV should only be used to rapidly increase sedation in patients who are not at risk for hypotension. The mean infusion rate required to maintain adequate sedation during clinical trials was 27 mcg/kg/minute (1.6 mg/kg/hour) IV. Infusion rates were lower in patients older than 55 years (approximately 20 mcg/kg/minute [1.2 mg/kg/hour]) compared to those younger than 55 years (approximately 38 mcg/kg/minute [2.3 mg/kg/hour]). Maintenance dosages were generally higher for patients with acute respiratory distress syndrome or respiratory failure than for other critically ill populations. Maintenance infusion rates were generally low (median: 11 mcg/kg/minute) in post-CABG patients due to the intraoperative administration of high opioid doses. Evaluate clinical effects and CNS function daily to determine minimum effective dosage. Individualize dosage based on patient's condition and response, serum lipid profile, and vital signs. Do not abruptly discontinue for weaning or sedation assessment. Rapid awakening may be associated with anxiety, agitated state, and resistance to mechanical ventilation. Maintain a light sedation level throughout the weaning process until 10 to 15 minutes before extubation.

    Infants, Children, and Adolescents 16 years and younger

    Not recommended. Propofol is not indicated for sedation in the pediatric intensive care unit (PICU) and should not be used for this purpose. There have been anecdotal reports of serious adverse events and death of children who received propofol for PICU sedation.

    For monitored anesthesia care sedation.
    For initiation of monitored anesthesia care sedation.
    Continuous Intravenous Infusion dosage
    Adults and Adolescents 17 years and older

    100 to 150 mcg/kg/minute (6 to 9 mg/kg/hour) IV infusion over 3 to 5 minutes in healthy adults age 54 years or less, titrated to clinical response and followed immediately by maintenance dosing. Reduce the dosage to approximately 80% of the usual adult dosage in elderly, debilitated, neurosurgical, or ASA-PS III or IV patients according to their condition, responses, and changes in vital signs. Closely monitor cardiorespiratory function.

    Intermittent Intravenous dosage
    Adults and Adolescents 17 years and older

    0.5 mg/kg slow IV injection over 3 to 5 minutes in healthy adults age 54 years or less, titrated to clinical response and followed immediately by maintenance dosing. Reduce the dosage to approximately 80% of the usual adult dosage in elderly, debilitated, neurosurgical, or ASA-PS III or IV patients according to their condition, responses, and changes in vital signs; avoid rapid (single or repeated) bolus dose administration in these patient populations. Closely monitor cardiorespiratory function.

    For maintenance of monitored anesthesia care sedation.
    Continuous Intravenous Infusion dosage
    Adults and Adolescents 17 years and older

    25 to 75 mcg/kg/minute (1.5 to 4.5 mg/kg/hour) IV continuous infusion is required in most healthy adults age 54 years or less during the first 10 to 15 minutes of maintenance. Subsequently decrease the infusion rate to 25 to 50 mcg/kg/minute IV and adjust according to clinical response, allowing approximately 2 minutes for onset of peak drug effect. Titrate infusion rates downward in the absence of clinical signs of light sedation until mild responses to stimulation are obtained in order to avoid administration at rates higher than are clinically necessary. Reduce the dosage and rate of administration to approximately 80% of the usual adult dosage in elderly, debilitated, neurosurgical, or ASA-PS III or IV patients according to their condition, responses, and changes in vital signs. Closely monitor cardiorespiratory function.

    Intermittent Intravenous dosage
    Adults and Adolescents 17 years and older

    A variable rate intravenous infusion is preferred over an intermittent bolus technique. If bolus dosing is utilized, administer 10 or 20 mg/dose IV as incremental boluses in healthy adults age 54 years or less. Reduce the dosage to approximately 80% of the usual adult dosage in elderly, debilitated, neurosurgical, or ASA-PS III or IV patients according to their condition, responses, and changes in vital signs; avoid rapid (single or repeated) bolus dose administration in these patient populations. Titrate dosage to clinical effect. Closely monitor cardiorespiratory function.

    For the treatment of refractory status epilepticus†.
    Intravenous dosage
    Adults

    Although a definitive dosage has not been established, a loading dose of 1 to 2 mg/kg IV, followed by 2 to 10 mg/kg/hour IV as a continuous infusion has been recommended to induce anesthesia in patients with refractory status epilepticus. The maintenance dose is usually continued for 12 to 24 hours and adjusted according to EEG results. The primary end-point is EEG burst suppression. After 12 to 24 hours, the continuous infusion of propofol is withdrawn gradually. If seizures recur, therapy should be resumed for progressively longer periods, as needed.

    For the treatment of refractory migraine†.
    NOTE: Due to the anesthetic doses required, propofol should only be administered by an anesthetic care team.
    Intravenous dosage
    Adults

    Propofol administration to induce unconsciousness has reduced migraine pain upon awakening. Pain from three refractory headaches was greatly reduced by 0.5—1 mg/kg IV of propofol in one patient, although treatment of two headaches required repeat propofol administration at the same dosage.

    For post-operative nausea/vomiting (PONV) prophylaxis†.
    NOTE: The antiemetic effect of propofol is greatest during the infusion with an increased risk of nausea and vomiting after drug administration cessation.
    NOTE: Prevention of nausea and vomiting appears to be associated with a plasma propofol concentration between 280 and 530 ng/mL.
    Intravenous dosage
    Adults

    Use of subhypnotic doses of propofol (0.5 mg/kg IV) at surgery completion helps reduce nausea/vomiting; the effect of a concomitant 5-HT3 receptor antagonist is currently unknown. Administration of propofol in a subanesthetic dose (10 mg IV) produced significant symptomatic improvement in nausea/vomiting as compared to placebo-treated patients. However, relapse occurred at a similar rate to the placebo group. Propofol 20 mg IV given by patient-controlled device with a 5 minute lockout period significantly reduced the average nausea score, emesis episodes, and need for rescue antiemetic therapy as compared to the placebo-treated group. Use of a 0.1 to 0.2 mg/kg IV bolus followed by a 1 mg/kg/hour IV infusion of propofol helps prevent and treat chemotherapy-associated nausea/vomiting that is inadequately treated with serotonin antagonists or dexamethasone. Fewer patients that received propofol for induction (2 mg/kg) and maintenance (50 to 150 mcg/kg/minute infusion) of anesthesia versus isoflurane vomited (19%) within 6 hours of surgery than did patients that received ondansetron (48%), propofol for induction only (64%), or propofol for only the last 30 minutes of anesthesia maintenance (52%). Antiemetic use and sedation scores were also significantly lower for the group that received propofol throughout the procedure.

    For the treatment of agitation† associated with alcohol withdrawal.
    Intravenous dosage
    Adults

    Continuous infusions of propofol controlled agitation and other symptoms of alcohol withdrawal, such as diaphoresis, tremors, and delirium in 4 patients that had a suboptimal response to benzodiazepines. Propofol was titrated to a rate (40—90 mcg/kg/minute IV) that achieved sedation with rousability to a light tactile stimulus. Daily attempts were made to wean the dose; patients received propofol for 4—11 days.

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

    1 to 1.5 mg/kg IV load, followed by 0.25 to 0.5 mg/kg/dose IV every 3 to 5 minutes as needed. When given in conjunction with ketamine, the dosage should be reduced (i.e., 0.5 to 0.75 mg/kg IV load). Alternatively, a continuous infusion of 50 to 150 mcg/kg/minute (3 to 9 mg/kg/hour) IV may be administered. Closely monitor cardiorespiratory status.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    Specific maximum dosage information not available; dose required is dependent on indication and clinical response.

    Geriatric

    Specific maximum dosage information not available; dose required is dependent on indication and clinical response.

    Adolescents

    Specific maximum dosage information not available; dose required is dependent on indication and clinical response.

    Children

    3 to 12 years: Specific maximum dosage information not available; dose required is dependent on indication and clinical response.
    1 to 2 years: Specific maximum dosage information not available; dose required for anesthesia maintenance is dependent on clinical response. Propofol is not indicated for anesthesia induction in this age group.

    Infants

    2 to 11 months: Specific maximum dosage information not available; dose required for anesthesia maintenance is dependent on clinical response. Propofol is not indicated for anesthesia induction in this age group.
    1 month: Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    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

    Injectable Administration

    Only administer by intravenous (IV) administration by individuals trained in the administration of general anesthetics when used for general anesthesia or monitored anesthesia care sedation.
    Although not a controlled substance, propofol has been abused. Access restriction and accounting procedures are recommended.
    Strict aseptic technique must be followed during handling as the lipid-based vehicle is capable of supporting rapid growth of microorganisms. Disinfect the rubber stopper of the vial or prefilled syringe with 70% isopropyl alcohol.
    Prepare immediately before use. Use a sterile vent spike to draw out of a vial into a sterile syringe. Label the syringe with the time and date the vial was opened.
    Filters should be used with caution and only where clinically appropriate. If in-line filters are used, they must be at least 5 micron. Smaller pores may cause emulsion instability or clog tubings. Continuous monitoring is necessary because of the potential for restricted flow and emulsion breakdown. Do not use if there is evidence of separation of the phases of the emulsion.
    Shake well before using. Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Propofol emulsions are milky white, which makes it difficult to detect contaminates. If the emulsion appears to be separated, do not use.
    Propofol (Diprivan): Diprivan has 0.005% disodium edetate to retard the growth of microorganisms in the event of accidental extrinsic contamination. Propofol is not an antimicrobially preserved product under USP standards. To minimize the potential for bacterial contamination, use a vial for only one patient, and begin drug administration immediately after the vial has been opened. Administration for ICU sedation directly from the vial must be completed within 12 hours of spiking the vial; discard tubing and any unused portion after 12 hours. If transferred to a syringe or other container before administration for ICU sedation, discard unused portions and IV lines at the end of the procedure or within 12 hours of opening the Diprivan vial, whichever is sooner. For general anesthesia or procedural sedation, draw into sterile syringes immediately after opening the vials. After vial is spiked, complete administration within 12 hours for Diprivan. Discard unused portions, reservoir, dedicated administration tubing, and solutions containing propofol at the end of the procedure or within 12 hours of opening the Diprivan vial, whichever is sooner. Flush the IV line every 12 hours for Diprivan and at the end of the anesthesia procedure.
    Generic propofol: Generic propofol has sodium metabisulfite or benzyl alcohol and sodium benzoate to retard the growth of microorganisms in the event of accidental extrinsic contamination. Propofol is not an antimicrobially preserved product under USP standards. To minimize the potential for bacterial contamination, use a vial for only one patient, and begin drug administration immediately after the vial has been opened. Administration for ICU sedation directly from the vial must be completed within 12 hours of spiking the vial; discard tubing and any unused portion after 12 hours. If transferred to a syringe or other container before administration for ICU sedation, discard unused portions and IV lines at the end of the procedure or within 6 hours of opening the generic propofol vial, whichever is sooner. For general anesthesia or procedural sedation, draw into sterile syringes immediately after opening the vials. After vial is spiked, complete administration within 6 hours for generic propofol. Discard unused portions, reservoir, dedicated administration tubing, and solutions containing propofol at the end of the procedure or within 6 hours of opening the generic propofol vial, whichever is sooner. Flush the IV line every 6 hours for generic propofol and at the end of the anesthesia procedure.

    Intravenous Administration

    Dilution
    Dilution is not necessary, but if desired, use only 5% Dextrose Injection. The concentration should be no less than 2 mg/mL.
    Diluted propofol is more stable when in contact with glass than with plastic.
    Do not mix with other agents before administration. If lidocaine is to be administered to minimize injection-related pain, administer lidocaine before or add it to propofol immediately before propofol administration in quantities not exceeding 20 mg lidocaine per 200 mg propofol. An instability of the Diprivan emulsion has been reported with lidocaine addition in quantities greater than 20 mg per 200 mg of Diprivan.
     
    Intermittent IV Injection
    Shake propofol well before using.
    Inject IV over 3 to 5 minutes and titrate to desired level of sedation.
     
    Continuous IV Infusion
    Shake well before using.
    Administer only by persons skilled in the medical management of critically ill patients and trained in cardiovascular resuscitation and airway management.
    Diprivan and generic propofol are compatible with the following intravenous fluids when administered through a y-type infusion set: 5% Dextrose Injection, Lactated Ringer's Injection, 5% Dextrose and Lactated Ringer's Injection, 5% Dextrose and 0.45% Sodium Chloride Injection, and 5% Dextrose and 0.2% Sodium Chloride Injection.
    The dose and rate of administration must be individualized.
    Do not administer through the same IV catheter with blood or plasma. Compatibility has not been established and aggregates of the globular component of the emulsion vehicle with blood/plasma/serum have been noted in vitro.
    Do not infuse Diprivan more than 5 days in a row. A drug holiday is needed to replace estimated or measured zinc losses from chelation from EDTA.
    Syringe pumps or volumetric pumps are recommended to provide controlled infusion rates.

    STORAGE

    Diprivan:
    - Discard unused portion. Do not store for later use.
    - Do not freeze
    - Store between 40 to 77 degrees F
    Fresenius Propoven :
    - Discard unused portion. Do not store for later use.
    - Do not freeze
    - Store between 40 to 77 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Failure to use strict aseptic technique when handling propofol has been associated with microbial contamination and patient fever, infection, and death. Do not use propofol if contamination is suspected. Antibacterial additives (e.g., EDTA, sodium metabisulfite) may retard the growth rate of microorganisms for up to 12 hours; discard any unused portions within the required time limits. Monitor all patients closely for signs and symptoms of bacterial infection.

    Asthma, benzyl alcohol hypersensitivity, egg hypersensitivity, soya lecithin hypersensitivity, sulfite hypersensitivity

    Propofol is contraindicated for use when general anesthesia or sedation is contraindicated. Propofol is also contraindicated in patients with hypersensitivity to the drug or to any of the components. Propofol emulsions contain soybean oil and egg yolk phospholipid or egg lecithin and thus, should not be used in patients with egg hypersensitivity or soya lecithin hypersensitivity. Some propofol formulations additionally contain sodium metabisulfite, sodium benzoate, or benzyl alcohol. Patients with benzyl alcohol hypersensitivity should not receive propofol emulsion formulations that contain benzyl alcohol. Similarly, patients with sulfite hypersensitivity should not receive propofol formulations that contain sodium metabisulfite; sulfite sensitivity is seen more frequently in patients with asthma. Check product ingredients if patients have a history of these sensitivities. There are a number of products that are preservative-free.

    Extravasation

    Extravasation of propofol may cause local pain, swelling, blisters, and tissue necrosis. Propofol is directly irritating to the venous intima. Propofol also activates the kallikrein-kinin system, which results in bradykinin production. Bradykinin dilates and increases the permeability of the vein. As a result, the aqueous-phase propofol irritates more free nerve endings outside the endothelial layer of the vessel. Extravasation of propofol should be avoided. Patients should be closely monitored during IV infusions for signs and symptoms of extravasation.

    Sepsis

    There have been reports in which failure to use aseptic technique when handling propofol emulsion was associated with microbial contamination of the product and with fever, infection, sepsis, other life-threatening illness, and death. The emulsion can readily support the growth of microorganisms. Do not use if contamination is suspected. Discard unused portions as directed within the required time limits to limit the risk for sepsis.

    Cardiac disease, dehydration, heart failure, hypotension, hypovolemia, obesity, pulmonary disease

    Use propofol with caution in patients with cardiac disease, heart failure, intravascular volume depletion (e.g., hypovolemia, dehydration), abnormally low vascular tone (e.g., sepsis), or hemodynamic instability (e.g., heart failure). Patients with these conditions may be more susceptible to propofol-induced hypotension. A lower induction dose and slower maintenance rate should be used in such patients and any patient with severe systemic disease (ASA-PS III or IV). Consider the risk of hemodynamic effects on the cardiovascular system in patients who are severely overweight (obesity), as the propofol dosage will be higher. Compensate for cardiac, circulatory, and pulmonary disease or insufficiency and correct fluid deficits prior to propofol administration. If fluid therapy is contraindicated, other measures (e.g., lower extremity elevation, vasopressor initiation) may be used to offset hypotension. Adjust infusion rates slowly and avoid rapid boluses in order to minimize hypotension. If hypotension occurs, it may be responsive to drug discontinuation, IV fluid administration, and/or vasopressor therapy.

    Cerebrovascular disease, electroconvulsive therapy (ECT), increased intracranial pressure, seizure disorder

    Patients with a seizure disorder may be at risk of developing a seizure during the recovery phase. Propofol should also be used cautiously in patients with cerebrovascular disease, impaired cerebral blood flow, or increased intracranial pressure because propofol can cause a significant reduction in mean arterial pressure and thus, cerebral perfusion. Check that the patient has received a medicine for seizures before anesthesia receipt. Also, use of Fresenius Propoven 1% with electroconvulsive therapy (ECT) is not recommended.

    Hyperlipidemia, hyperlipoproteinemia, pancreatitis

    Disorders of lipid metabolism can be aggravated by the emulsion vehicle in which propofol is delivered. Propofol is an oil-in-water emulsion that provides 0.1 gram of fat (1.1 kcal) per mL. Increases in the serum triglyceride concentration can occur with prolonged propofol administration. If fat is inadequately cleared from the body, propofol dosage adjustment may be needed. Thus, propofol should be used cautiously in patients with diabetic hyperlipidemia, pancreatitis, or primary hyperlipoproteinemia and in those receiving lipids as part of a total parenteral nutrition regimen. Serum lipids, pancreatic enzymes, and glucose may need to be monitored.

    Geriatric

    Geriatric or debilitated patients are typically more sensitive to the effects of propofol than are younger patients. Elderly patients likely have reduced total body clearance and volume of distribution of propofol and should be given lower induction doses and slower infusion rates for anesthesia maintenance.

    Breast-feeding

    The manufacturer does not recommend propofol for use in nursing mothers. However, other experts state that in general, healthy term infants can safely nurse after a surgical procedure, as soon as the mother is awake and alert. Propofol is minimally excreted into breast milk, and the oral bioavailability to nursing infant is likely to be very low. Propofol is highly protein bound (>= 98%). 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. The risk to an infant after prolonged maternal exposure is less clear. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Brain tumor, children, head trauma, infants, stroke

    Safety and dosing requirements for induction and maintenance of anesthesia in pediatric patients have been established for children at least 3 years of age and infants at least 2 months of age, respectively. Adverse events associated with propofol are similar between children and adults, although more children appear to experience apnea. Propofol is not recommended for sedation of neonates, infants, children, or adolescents younger than 17 years of age in the pediatric intensive care unit (PICU) and should not be used for this purpose. More deaths were reported for pediatric patients who received propofol for sedation in the PICU as compared to patients who received standard sedative agents. Careful review of the deaths failed to reveal a correlation with underlying disease status or a definite pattern to the causes of death. In another study, propofol administration at a rate of less than 50 mcg/kg/minute to 142 children between the ages of 2 months and 18 years was not associated with any serious adverse events. Most of the children were mechanically ventilated (97%) and received propofol for less than 48 hours. A propofol infusion syndrome in children has been described consisting of myocardial infarction, metabolic acidosis, and rhabdomyolysis. There was a significant association between high-dose, long-term propofol therapy and development of progressive heart failure, although a causative relationship could not be proven. A similar syndrome has also been reported in adults. Risk factors for these events may include the use of high-dose propofol (more than 5 mg/kg/hour) and the presence of head trauma. Patients with head injury may receive higher propofol doses to control intracranial pressure. Additionally, vasopressor administration to maintain an adequate cerebral perfusion pressure may aggravate or precipitate cardiac failure or metabolic acidosis. Vasopressor use may also compromise splanchnic blood flow, which could result in elevated propofol concentrations. After propofol receipt, a risk of a significant decrease of the intracerebral perfusion pressure exists in patients who have a high intracranial pressure and a low mean arterial pressure. Examples of such patients may include those with head injury, brain tumor, or stroke.

    Labor, obstetric delivery, pregnancy

    Propofol is classified in FDA pregnancy category B. There are no adequate and well-controlled studies of propofol use in pregnant women. According to the manufacturer, 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.

    Abrupt discontinuation

    Abrupt discontinuation for weaning or sedation assessment is not recommended. Rapid awakening may be associated with anxiety, agitation, tremulousness, and resistance to mechanical ventilation. Maintain a light sedation level throughout the weaning process until 10—15 minutes before extubation. Following prolonged infusion in pediatric patients, abrupt discontinuation was associated with a higher incidence of bradycardia (5%), agitation (4%), and jitteriness (9%). Propofol withdrawal syndrome has been described in a burn patient receiving propofol as a continuous IV infusion for 95 days. The patient received propofol infusions ranging from 5—35 mcg/kg/min to control extreme agitation that was complicating ventilator weaning. Repeated attempts to taper the propofol were associated with withdrawal symptoms such as extreme agitation, tremors, tachycardia, tachypnea, and hyperpyrexia. Seizures have also been reported in other cases during propofol withdrawal. Standard weaning protocols for propofol are not available. In one case, the manufacturer recommended to taper propofol infusions in increments of 0.25 mcg/kg/min or 0.1 ml/hour using a pediatric infusion pump. It has also been suggested to reduce propofol infusion rates in patients who exhibit withdrawal by roughly 10% every 6 hours, as tolerated.

    Burns, diarrhea

    Patients with diarrhea, burns, or sepsis are predisposed to zinc deficiency. A chelator of zinc, disodium edetate (EDTA), is found in one of the propofol formulations, Diprivan. The mean daily urinary zinc loss in adults and pediatric patients enrolled in clinical trials was 2.5—3 mg and 1.5—2 mg, respectively. Zinc supplementation should be considered for patients predisposed to zinc deficiency that will receive prolonged administration of propofol. Administration of propofol for more than 5 days is not recommended without providing a drug holiday to safely replace estimated or measured urine zinc losses.

    Renal disease, renal failure, renal impairment

    As EDTA (2—3 grams/day) can also be toxic to the renal tubules, prolonged administration of Diprivan should be used with caution in patients with renal impairment or renal failure, and in those at risk for renal impairment, such as patients with renal disease. No change in renal function has been noted in patients enrolled in clinical trials that received propofol with 0.005% EDTA. However, urinalysis and urine sediment before propofol administration and every other day during therapy is recommended for patients at risk for renal impairment. Generic propofol does not contain EDTA.

    Driving or operating machinery

    After propofol receipt, the patient should avoid driving or operating machinery. Observe the patient for an appropriate time period, and ensure that the patient is escorted home and told to avoid alcohol.

    Requires a specialized care setting, requires an experienced clinician

    Propofol administration requires an experienced clinician skilled in the use of general anesthesia and not involved in the conduct of the surgical or diagnostic procedure for which propofol is being used. Additionally, propofol administration requires a specialized care setting; facilities for airway maintenance, assisted ventilation, supplemental oxygen, and cardiovascular resuscitation must be immediately available. Clinicians should be trained in cardiovascular resuscitation and airway management. For sedation of intubated, mechanically ventilated patients in the intensive care unit, propofol should only be administered by those skilled in the management of such patients. Patients should be continuously monitored for early signs of hypotension, apnea, airway obstruction, and oxygen desaturation. Cardiorespiratory effects are more likely to occur after rapid bolus administration, especially in elderly, debilitated, or ASA-PS III or IV patients.

    Substance abuse

    Propofol has the potential for substance abuse. Instances of self-administration in health care professionals have been reported. Injury and death have resulted from improper or recreational use. Although propofol is not a controlled substance, it is recommended inventory have restricted access and accounting procedures, as appropriate to the clinical setting, to prevent the risk of diversion.

    ADVERSE REACTIONS

    Severe

    apnea / Delayed / 1.0-43.0
    bradycardia / Rapid / 1.0-3.0
    arrhythmia exacerbation / Early / 0-3.0
    ventricular fibrillation / Early / 0-1.0
    myocardial infarction / Delayed / 0-1.0
    heart failure / Delayed / 0-1.0
    ventricular tachycardia / Early / 0-1.0
    cardiac arrest / Early / 0-1.0
    AV block / Early / 0-1.0
    atrial fibrillation / Early / 0-1.0
    seizures / Delayed / 0-1.0
    increased intracranial pressure / Early / 0-1.0
    thrombosis / Delayed / 0-1.0
    laryngospasm / Rapid / 0-1.0
    pulmonary edema / Early / 0-1.0
    anaphylactoid reactions / Rapid / 0-1.0
    bronchospasm / Rapid / 0-1.0
    hyperkalemia / Delayed / 0-1.0
    ileus / Delayed / 0-1.0
    oliguria / Early / 0-1.0
    renal failure (unspecified) / Delayed / 0-1.0
    asystole / Rapid / Incidence not known
    atrial tachycardia / Early / Incidence not known
    tissue necrosis / Early / Incidence not known
    angioedema / Rapid / Incidence not known
    pancreatitis / Delayed / Incidence not known
    pulmonary hypertension / Delayed / Incidence not known
    rhabdomyolysis / Delayed / Incidence not known

    Moderate

    hypotension / Rapid / 3.0-26.0
    myoclonia / Delayed / 3.0-17.0
    hypertension / Early / 0-8.0
    sinus tachycardia / Rapid / 0-3.0
    edema / Delayed / 0-1.0
    hypoventilation / Rapid / 0-1.0
    ST-T wave changes / Rapid / 0-1.0
    supraventricular tachycardia (SVT) / Early / 0-1.0
    dyspnea / Early / 0-1.0
    tachypnea / Early / 0-1.0
    premature ventricular contractions (PVCs) / Early / 0-1.0
    chest pain (unspecified) / Early / 0-1.0
    hypoxia / Early / 0-1.0
    bundle-branch block / Early / 0-1.0
    dystonic reaction / Delayed / 0-1.0
    delirium / Early / 0-1.0
    confusion / Early / 0-1.0
    depression / Delayed / 0-1.0
    hypertonia / Delayed / 0-1.0
    euphoria / Early / 0-1.0
    hypotonia / Delayed / 0-1.0
    peripheral neuropathy / Delayed / 0-1.0
    hallucinations / Early / 0-1.0
    phlebitis / Rapid / 0-1.0
    wheezing / Rapid / 0-1.0
    erythema / Early / 0-1.0
    elevated hepatic enzymes / Delayed / 0-1.0
    metabolic acidosis / Delayed / 0-1.0
    hypomagnesemia / Delayed / 0-1.0
    hyperglycemia / Delayed / 0-1.0
    dehydration / Delayed / 0-1.0
    conjunctival hyperemia / Early / 0-1.0
    nystagmus / Delayed / 0-1.0
    amblyopia / Delayed / 0-1.0
    urinary retention / Early / 0-1.0
    bleeding / Early / 0-1.0
    respiratory depression / Rapid / Incidence not known
    hypertriglyceridemia / Delayed / Incidence not known
    hepatomegaly / Delayed / Incidence not known
    hyperlipidemia / Delayed / Incidence not known
    zinc deficiency / Delayed / Incidence not known
    withdrawal / Early / Incidence not known

    Mild

    rash (unspecified) / Early / 0-5.0
    pruritus / Rapid / 0-3.0
    syncope / Early / 0-1.0
    hyperventilation / Early / 0-1.0
    dizziness / Early / 0-1.0
    premature atrial contractions (PACs) / Early / 0-1.0
    tremor / Early / 0-1.0
    anxiety / Delayed / 0-1.0
    paresthesias / Delayed / 0-1.0
    emotional lability / Early / 0-1.0
    headache / Early / 0-1.0
    insomnia / Early / 0-1.0
    drowsiness / Early / 0-1.0
    shivering / Rapid / 0-1.0
    agitation / Early / 0-1.0
    urticaria / Rapid / 0-1.0
    diaphoresis / Early / 0-1.0
    flushing / Rapid / 0-1.0
    chills / Rapid / 0-1.0
    fever / Early / 0-1.0
    myalgia / Early / 0-1.0
    xerostomia / Early / 0-1.0
    hypersalivation / Early / 0-1.0
    vomiting / Early / 0-1.0
    nausea / Early / 0-1.0
    dysgeusia / Early / 0-1.0
    diarrhea / Early / 0-1.0
    ocular pain / Early / 0-1.0
    diplopia / Early / 0-1.0
    tinnitus / Delayed / 0-1.0
    urine discoloration / Early / 0-1.0
    leukocytosis / Delayed / 0-1.0
    hiccups / Early / 0-1.0
    weakness / Early / 0-1.0
    sneezing / Early / 0-1.0
    pharyngitis / Delayed / 0-1.0
    asthenia / Delayed / 0-1.0
    fatigue / Early / 0-1.0
    cough / Delayed / 0-1.0
    injection site reaction / Rapid / 10.0
    infection / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Butalbital: Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
    Acetaminophen; Butalbital; Caffeine: Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
    Acetaminophen; Butalbital; Caffeine; Codeine: Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: 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. Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: 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. Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Acetaminophen; Dextromethorphan; Doxylamine: Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: 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: 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: Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Acetaminophen; Guaifenesin; Phenylephrine: 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: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone 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. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include general anesthetics.
    Acetaminophen; Oxycodone: Concomitant use of oxycodone with other CNS depressants, such as general anesthetics, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone 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. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression.
    Acetaminophen; Tramadol: Tramadol can cause additive CNS depression and respiratory depression when used with other agents that are CNS depressants, such as general anesthetics. A reduced dose of tramadol is recommended when used with another CNS depressant.
    Acrivastine; Pseudoephedrine: Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Aliskiren: 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: 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: 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: 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: 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: 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: Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving amikacin.
    Amiodarone: 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: General anesthetics like propofol may produce additive CNS depression when used in patients taking tricyclic antidepressants.
    Amitriptyline; Chlordiazepoxide: General anesthetics like propofol may produce additive CNS depression when used in patients taking tricyclic antidepressants.
    Amobarbital: Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
    Amoxapine: Because amoxapine can cause sedation, an enhanced CNS depressant effect may occur during combined use with general anesthetics such as enflurane.
    Amphetamine: 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: 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: 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: General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Angiotensin-converting enzyme inhibitors: General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Apomorphine: Apomorphine causes significant somnolence. Concomitant administration of apomorphine and CNS depressants could result in additive depressant effects.
    Apraclonidine: 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: 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: Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
    Aspirin, ASA; Carisoprodol: General anesthetics poteniate the effect of other CNS depreesants including carisoprodol.
    Aspirin, ASA; Carisoprodol; Codeine: General anesthetics poteniate the effect of other CNS depreesants including carisoprodol.
    Aspirin, ASA; Oxycodone: Concomitant use of oxycodone with other CNS depressants, such as general anesthetics, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone 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. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression.
    Atracurium: Increased neuromuscular blockade may occur if general anesthetics are used with nondepolarizing neuromuscular blockers.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
    Azelastine: An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including general anesthetics.
    Azelastine; Fluticasone: An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including general anesthetics.
    Bacitracin: 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: Concomitant use of skeletal muscle relaxants with other CNS depressants like general anesthetics can result in additive CNS depression.
    Barbiturates: Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
    Benzodiazepines: Concomitant administration can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent.
    Benzonatate: Propofol potentiates CNS depression and may enhance the sedative, respiratory depressive, and hypotensive effects of local anesthetics. A reduced dose of propofol may be needed for induction if it is used in conjunction with other medications that cause CNS depression.
    Benzphetamine: 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: 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: Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Brompheniramine; Carbetapentane; Phenylephrine: 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. 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. Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Brompheniramine; Dextromethorphan; Guaifenesin: Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Brompheniramine; Guaifenesin; Hydrocodone: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone 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. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include general anesthetics. Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Brompheniramine; Hydrocodone; Pseudoephedrine: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone 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. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include general anesthetics. Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Brompheniramine; Pseudoephedrine: Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Bupivacaine Liposomal: 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. 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 halogenated anesthetics.
    Bupivacaine: 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. 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 halogenated anesthetics.
    Bupivacaine; Lidocaine: 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. 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 halogenated anesthetics.
    Buspirone: General anesthetics potentiate the effects of CNS depressants.
    Butabarbital: Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
    Butorphanol: Concomitant use of butorphanol with other CNS depressants can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
    Calcium-channel blockers: 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.
    Capreomycin: 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: General anesthetics potentiate the effects of other CNS depressants, including skeletal muscle relaxants.
    Carbetapentane; Chlorpheniramine: 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. Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Carbetapentane; Chlorpheniramine; Phenylephrine: 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. 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. Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Carbetapentane; Diphenhydramine; Phenylephrine: 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. 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. Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Carbetapentane; Guaifenesin: 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: 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. 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: 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. 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: 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. 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. Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Carbetapentane; Pseudoephedrine: 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: 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. Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Carbidopa; Levodopa: 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: 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: Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Carbinoxamine; Hydrocodone; Phenylephrine: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone 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. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include general anesthetics. 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. Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone 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. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include general anesthetics. Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Carbinoxamine; Phenylephrine: 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. Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Carbinoxamine; Pseudoephedrine: Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Carisoprodol: General anesthetics poteniate the effect of other CNS depreesants including carisoprodol.
    Central-acting adrenergic agents: General anesthetics can potentiate the hypotensive effects of antihypertensive agents. Reduced dosages of antihypertensives may be required during heavy sedation.
    Cetirizine: Additive drowsiness may occur if cetirizine/levocetirizine is administered with other drugs that depress the CNS, such as general anesthetics.
    Cetirizine; Pseudoephedrine: Additive drowsiness may occur if cetirizine/levocetirizine is administered with other drugs that depress the CNS, such as general anesthetics.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Chlophedianol; Guaifenesin; Phenylephrine: 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: Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Chloroprocaine: 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: Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Chlorpheniramine; Codeine: Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Chlorpheniramine; Dextromethorphan: Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: 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. Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: 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. Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone 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. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include general anesthetics. Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Chlorpheniramine; Hydrocodone: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone 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. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include general anesthetics. Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Chlorpheniramine; Hydrocodone; Phenylephrine: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone 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. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include general anesthetics. 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. Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone 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. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include general anesthetics. Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Chlorpheniramine; Phenylephrine: 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. Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Chlorpheniramine; Pseudoephedrine: Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Cholinesterase inhibitors: 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.
    Cisatracurium: Increased neuromuscular blockade may occur if general anesthetics are used with nondepolarizing neuromuscular blockers.
    Clemastine: Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Clobazam: 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: General anesthetics like propofol may produce additive CNS depression when used in patients taking tricyclic antidepressants.
    Clozapine: 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; Phenylephrine; Promethazine: 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.
    Cyclizine: Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Cyproheptadine: Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Dantrolene: General anesthetics potentiate the effects of other CNS depressants, including skeletal muscle relaxants.
    Desipramine: General anesthetics like propofol may produce additive CNS depression when used in patients taking tricyclic antidepressants.
    Dexchlorpheniramine: Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Dexmedetomidine: Co-administration of dexmedetomidine with general anesthetics is likely to lead to an enhancement of CNS depression.
    Dextroamphetamine: 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: 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. Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Dextromethorphan; Guaifenesin; Phenylephrine: 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: 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.
    Dimenhydrinate: Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Diphenhydramine: Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Diphenhydramine; Hydrocodone; Phenylephrine: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone 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. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include general anesthetics. 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. Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Diphenhydramine; Ibuprofen: Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Diphenhydramine; Phenylephrine: 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. Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Dopamine: 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.
    Doxacurium: Increased neuromuscular blockade may occur if general anesthetics are used with nondepolarizing neuromuscular blockers.
    Doxazosin: General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Doxepin: General anesthetics like propofol may produce additive CNS depression when used in patients taking tricyclic antidepressants.
    Doxylamine: Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Doxylamine; Pyridoxine: Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Dronabinol, THC: Concomitant use of dronabinol with other CNS depressants like general anesthetics can potentiate the effects of dronabinol on respiratory depression.
    Droperidol: 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: 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: Methylxanthines and inhaled general anesthetics have been associated with adverse cardiovascular effects. Concurrent use may increase the risk of such effects including cardiac arrhythmias.
    Enflurane: 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.
    Ephedrine: General anesthetics may sensitize the myocardium to the effects of sympathomimetics, including ephedrine.
    Epinephrine: 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: General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Epoprostenol: General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Eszopiclone: 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: Alcohol is associated with CNS depression. The combined use of alcohol and CNS depressants can lead to additive CNS depression, which could be dangerous in tasks requiring mental alertness and fatal in overdose. Alcohol taken with other CNS depressants can lead to additive respiratory depression, hypotension, profound sedation, or coma. Consider the patient's use of alcohol or illicit drugs when prescribing CNS depressant medications. In many cases, the patient should receive a lower dose of the CNS depressant initially if the patient is not likely to be compliant with avoiding alcohol.
    Etomidate: 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.
    Fentanyl: Concomitant use of fentanyl with other CNS depressants, such as general anesthetics, may cause respiratory depression, hypotension, and profound sedation; a coma could result. If concurrent use of fentanyl and a CNS depressant is desired, significantly reduce the dose of fentanyl and/or the other CNS depressant. Blood pressure and respiration monitoring to ensure the absence of hypotension and respiratory depression, respectively may be desirable.
    Gentamicin: Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving gentamicin.
    Guaifenesin; Hydrocodone: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone 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. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include general anesthetics.
    Guaifenesin; Hydrocodone; Pseudoephedrine: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone 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. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include general anesthetics.
    Guaifenesin; Phenylephrine: 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: 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.
    Halothane: 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.
    Homatropine; Hydrocodone: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone 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. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include general anesthetics.
    Hydrocodone: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone 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. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include general anesthetics.
    Hydrocodone; Ibuprofen: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone 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. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include general anesthetics.
    Hydrocodone; Phenylephrine: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone 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. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include general anesthetics. 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.
    Hydrocodone; Potassium Guaiacolsulfonate: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone 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. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include general anesthetics.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone 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. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include general anesthetics.
    Hydrocodone; Pseudoephedrine: Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone 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. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include general anesthetics.
    Hydromorphone: Concomitant use of hydromorphone with other central nervous system (CNS) depressants can potentiate the effects of hydromorphone and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include general anesthetics. Prior to concurrent use of hydromorphone 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. If hydromorphone is used concurrently with a CNS depressant, a reduced dosage of hydromorphone and/or the CNS depressant is recommended; start with one-third to one-half of the estimated hydromorphone starting dose when using hydromorphone extended-release tablets. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Hydroxyzine: Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Ibuprofen; Oxycodone: Concomitant use of oxycodone with other CNS depressants, such as general anesthetics, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone 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. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression.
    Iloprost: General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Imipramine: General anesthetics like propofol may produce additive CNS depression when used in patients taking tricyclic antidepressants.
    Iohexol: A higher incidence of adverse reactions has been reported with contrast media in anesthetized patients. This may be attributable to the inability of the patient to identify untoward symptoms, or to the hypotensive effect of anesthesia.
    Iopamidol: A higher incidence of adverse reactions has been reported with contrast media in anesthetized patients. This may be attributable to the inability of the patient to identify untoward symptoms, or to the hypotensive effect of anesthesia.
    Ioversol: A higher incidence of adverse reactions has been reported with contrast media in anesthetized patients. This may be attributable to the inability of the patient to identify untoward symptoms, or to the hypotensive effect of anesthesia.
    Isoproterenol: 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.
    Isosulfan Blue: A higher incidence of adverse reactions has been reported with contrast media in anesthetized patients. This may be attributable to the inability of the patient to identify untoward symptoms, or to the hypotensive effect of anesthesia.
    Kanamycin: 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.
    Levocetirizine: Additive drowsiness may occur if cetirizine/levocetirizine is administered with other drugs that depress the CNS, such as general anesthetics.
    Levodopa: 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: Concomitant use of levorphanol with other CNS depressants such as general anesthetics (propofol) can potentiate the effects of levorphanol on respiration, blood pressure, and alertness. Severe hypotension, respiratory depression, profound sedation, or coma may occur. Prior to concurrent use of levorphanol 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. When concomitant treatment with levorphanol with another CNS depressant is necessary, reduce the dose of 1 or both drugs. The initial dose of levorphanol should be reduced by approximately 50% or more when levorphanol is used with another drug that may depress respiration.
    Lisdexamfetamine: Inhalational general anesthetics may sensitize the myocardium to the effects of lisdexamfetamine. Dosages of the amphetamines should be substantially reduced prior to surgery, and caution should be observed with concurrent use of anesthetics.
    Loop diuretics: General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Loxapine: 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.
    Magnesium Salts: 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.
    Magnesium Sulfate; Potassium Sulfate; Sodium Sulfate: 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.
    Maprotiline: General anesthetics may produce additive CNS depression when used in patients taking maprotiline.
    Meclizine: Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Mephobarbital: Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
    Meprobamate: 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: General anesthetics potentiate the effects of other CNS depressants, including skeletal muscle relaxants.
    Methadone: 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: General anesthetics (e.g., enflurane, halothane, isoflurane, and methoxyflurane) may sensitize the myocardial conduction system to the action of sympathomimetics. Use extreme caution with the concomitant use of a general anesthetic and methamphetamine, as serious cardiac arrhythmias such as ventricular tachycardia or fibrillation may result.
    Methohexital: Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
    Midodrine: 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.
    Mifepristone, RU-486: Mifepristone, RU-486 inhibits CYP3A4 in vitro. Coadministration of mifepristone may lead to an increase in serum concentrations of drugs that are CYP3A4 substrates and that have a narrow therapeutic index, including the general anesthetics. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
    Minocycline: 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: Consistent with the pharmacology of mirtazapine and the drug's side effect profile, additive effects may occur with other CNS-active agents, including general anesthetics.
    Mivacurium: Increased neuromuscular blockade may occur if general anesthetics are used with nondepolarizing neuromuscular blockers.
    Monoamine oxidase inhibitors: Patients taking MAOIs should not undergo elective surgery, including dental procedures, that require the use of general anesthetics due to the potential for CNS and cardiovascular reactions. Combined hypotensive effects are possible with the combined use of MAOIs and spinal anesthetics. MAOIs should be discontinued for at least 10 days prior to elective surgery.
    Morphine: Concomitant use of morphine with other CNS depressants can potentiate the effects of morphine on respiration, blood pressure, and alertness. Prior to concurrent use of morphine 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. If a CNS depressant is used concurrently with morphine, a reduced dosage of morphine and/or the CNS depressant is recommended. Monitor patients for sedation and respiratory depression.
    Morphine; Naltrexone: Concomitant use of morphine with other CNS depressants can potentiate the effects of morphine on respiration, blood pressure, and alertness. Prior to concurrent use of morphine 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. If a CNS depressant is used concurrently with morphine, a reduced dosage of morphine and/or the CNS depressant is recommended. Monitor patients for sedation and respiratory depression.
    Nabilone: Concomitant use of nabilone with other CNS depressants like general anesthetics can potentiate the effects of nabilone on respiratory depression.
    Nalbuphine: Concomitant use of nalbuphine with other CNS depressants can potentiate the effects of nalbuphine on respiratory depression, CNS depression, and sedation.
    Nesiritide, BNP: The potential for hypotension may be increased when coadministering nesiritide with other hypotensive drugs, including general anesthetics.
    Neuromuscular blockers: Increased neuromuscular blockade may occur if general anesthetics are used with nondepolarizing neuromuscular blockers.
    Non-Ionic Contrast Media: A higher incidence of adverse reactions has been reported with contrast media in anesthetized patients. This may be attributable to the inability of the patient to identify untoward symptoms, or to the hypotensive effect of anesthesia.
    Norepinephrine: Norepinephrine interacts with general anesthetics because the anesthetics increase cardiac irritability, which can lead to arrhythmias.
    Nortriptyline: General anesthetics like propofol may produce additive CNS depression when used in patients taking tricyclic antidepressants.
    Orphenadrine: General anesthetics potentiate the effects of other CNS depressants, including skeletal muscle relaxants.
    Oxycodone: Concomitant use of oxycodone with other CNS depressants, such as general anesthetics, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone 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. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression.
    Oxymorphone: It has been reported that the incidence of bradycardia was increased when oxymorphone was combined with propofol for induction of anesthesia. Concomitant use of oxymorphone with other CNS depressants may produce additive CNS depressant effects. In some cases, hypotension, profound sedation, coma, respiratory depression, or death may occur. Severe hypotension may occur if a CNS depressant that inhibits blood pressure maintenance is used. Prior to concurrent use of oxymorphone 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. If a CNS depressant is used concurrently with oxymorphone, a reduced dosage of oxymorphone (1/3 to 1/2 of the usual dose) and/or the CNS depressant is recommended. If the extended-release oxymorphone tablets are used concurrently with a CNS depressant, it is recommended to use an initial dosage of 5 mg PO every 12 hours. Monitor for sedation or respiratory depression.
    Oxytocin: 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.
    Pancuronium: Increased neuromuscular blockade may occur if general anesthetics are used with nondepolarizing neuromuscular blockers.
    Papaverine: Concurrent use of papaverine with potent CNS depressants, such as general anesthetics, could lead to enhanced sedation.
    Pentobarbital: Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
    Perphenazine; Amitriptyline: General anesthetics like propofol may produce additive CNS depression when used in patients taking tricyclic antidepressants.
    Phenobarbital: Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
    Phenoxybenzamine: General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Phenylephrine: 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.
    Phenylephrine; Promethazine: 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.
    Polymyxins: General anesthetics can potentiate the neuromuscular blocking effect of colistimethate sodium by 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. However, much of this data was reported in early literature. Neurotoxicity is attributed to presynaptic action of colistin that interferes with receptor sites and blocks the release of acetylcholine.
    Potassium-sparing diuretics: General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Prazosin: General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Pregabalin: Concomitant administration of pregabalin with CNS depressant drugs, including general anesthetics, can potentiate the CNS effects of either agent.
    Prilocaine: 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: 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. 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: Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
    Procaine: 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: 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.
    Protriptyline: General anesthetics like propofol may produce additive CNS depression when used in patients taking tricyclic antidepressants.
    Rapacuronium: Increased neuromuscular blockade may occur if general anesthetics are used with nondepolarizing neuromuscular blockers.
    Rasagiline: 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: General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Ritodrine: The cardiovascular effects of sympathomimetics, especially hypotension and cardiac arrhythmias, can be potentiated by concomitant use of potent general anesthetics.
    Rocuronium: Increased neuromuscular blockade may occur if general anesthetics are used with nondepolarizing neuromuscular blockers.
    Secobarbital: Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
    Sedating H1-blockers: Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Sodium Oxybate: 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: General anesthetics can potentiate the antihypertensive effects of beta-blockers and can produce prolonged hypotension.
    St. John's Wort, Hypericum perforatum: 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: Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving streptomycin.
    Succinylcholine: Increased neuromuscular blockade may occur if general anesthetics are used with nondepolarizing neuromuscular blockers.
    Suvorexant: CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases. These agents include the general anesthetics.
    Tapentadol: Additive CNS depressive effects are expected if tapentadol is used in conjunction with other CNS depressants. Severe hypotension, profound sedation, coma, or respiratory depression may occur. Prior to concurrent use of tapentadol 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. If a CNS depressant is used concurrently with tapentadol, a reduced dosage of tapentadol and/or the CNS depressant is recommended. If the extended-release tapentadol tablets are used concurrently with a CNS depressant, it is recommended to use an initial tapentadol dose of 50 mg PO every 12 hours. Monitor patients for sedation and respiratory depression.
    Terazosin: General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Tetracaine: 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: Aminophylline used concurrently with inhaled general anesthetics may increase the risk of cardiac arrhythmias. 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: General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Thiopental: Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
    Thiothixene: 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: Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving tobramycin.
    Tramadol: Tramadol can cause additive CNS depression and respiratory depression when used with other agents that are CNS depressants, such as general anesthetics. A reduced dose of tramadol is recommended when used with another CNS depressant.
    Treprostinil: General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Tricyclic antidepressants: General anesthetics like propofol may produce additive CNS depression when used in patients taking tricyclic antidepressants.
    Trimipramine: General anesthetics like propofol may produce additive CNS depression when used in patients taking tricyclic antidepressants.
    Triprolidine: Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
    Trovafloxacin, Alatrofloxacin: General anesthetics may potentiate the hypotension associated alatrofloxacin administration.
    Tubocurarine: Increased neuromuscular blockade may occur if general anesthetics are used with nondepolarizing neuromuscular blockers.
    Valproic Acid, Divalproex Sodium: 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: The concurrent administration of vancomycin and anesthetics has been associated with erythema, histamine-like flushing, and anaphylactoid reactions.
    Vasodilators: General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Vecuronium: Increased neuromuscular blockade may occur if general anesthetics are used with nondepolarizing neuromuscular blockers.
    Warfarin: 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: 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: 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 classified in FDA pregnancy category B. There are no adequate and well-controlled studies of propofol use in pregnant women. According to the manufacturer, 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.

    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 and, due to its high lipophilicity, is rapidly distributed to all tissues in the body. There is fast equilibration between the plasma and the brain. Propofol crosses the placenta and is distributed into breast milk. Propofol is 95% to 99% protein-bound. The time to tissue saturation depends on the rate and duration of the infusion. 
     
    Propofol is metabolized in the liver where it rapidly undergoes glucuronide conjugation to inactive metabolites. Initially, the fall in plasma concentration is roughly 50% due to tissue distribution and 50% due to metabolic clearance. The steady state concentration is generally proportional to the infusion rate. The clearance of propofol exceeds estimated hepatic blood flow, which suggests extrahepatic routes of metabolism. The elimination half-life of 3 to 12 hours is the result of slow release of propofol from fat stores. About 70% of a single dose is excreted renally in 24 hours (90% in 5 days). The terminal half-life is 1 to 3 days after a 10-day infusion. Significant propofol accumulation may occur with long-term propofol use. Due to peripheral tissue saturation, the rate at which the propofol concentration will fall becomes more dependent on metabolic clearance than tissue redistribution.

    Intravenous Route

    After IV administration of propofol, loss of consciousness usually occurs within 40 seconds, although the onset of action varies with the dose, rate of administration, and extent of premedication. The duration of action of a 2 to 2.5 mg/kg bolus injection is 3 to 5 minutes despite a delayed release of drug from deep compartments.
     
    Recovery from anesthesia is rapid (8 to 19 minutes for 2 hours of anesthesia) and is associated with minimal psychomotor impairment. The time to awakening is affected by the tissue drug concentration. The longer the infusion, the greater time to awakening, which usually occurs at a propofol concentration of 0.5 mcg/mL or less. Emergence from light sedation (Ramsey score from 3 to 2) is usually less than 35 minutes if the infusion has lasted 3 days or less. The emergence time could be up to 3.5 hours or longer for patients that receive more than 3 days of propofol even if the sedation score is kept at 3. The more heavily sedated the patient, the longer the emergence time will likely be, especially for long infusion times. Longer emergence times may occur in obese patients.