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  • CLASSES

    Other General Anesthetics

    DEA CLASS

    Rx

    DESCRIPTION

    Short-acting sedative-hypnotic
    Used for general anesthesia during short procedures
    Rapid onset of action and recovery with minimal cardiac and respiratory-depressive effects, no histamine release

    COMMON BRAND NAMES

    Amidate

    HOW SUPPLIED

    Amidate/Etomidate Intravenous Inj Sol: 1mL, 2mg

    DOSAGE & INDICATIONS

    For general anesthesia induction.
    Intravenous dosage
    Adults

    0.2 to 0.6 mg/kg/dose IV over 30 to 60 seconds; usual dose = 0.3 mg/kg IV.

    Children and Adolescents 10 to 17 years

    0.2 to 0.6 mg/kg/dose IV over 30 to 60 seconds; usual dose = 0.3 mg/kg IV.

    For the supplementation of subpotent anesthetic agents (e.g., nitrous oxide) during general anesthesia maintenance for short operative procedures such as obstetric anesthesia for dilation and curettage or cervical conization.
    Intravenous dosage
    Adults

    0.2 to 0.6 mg/kg/dose IV over 30 to 60 seconds. Doses are usually less than those used for anesthesia induction; dosage must be individualized. There are insufficient data to support the use of etomidate for longer procedures. The use of intravenous fentanyl or other neuroactive agents during anesthesia may alter the dosage requirements of etomidate. Etomidate hypnosis does not significantly alter the usual dosage requirements of neuromuscular blocking agents employed for endotracheal intubation or other purposes shortly after induction of anesthesia.[49500]

    For sedation during rapid-sequence intubation†.
    NOTE: Etomidate is especially useful as a sedative in patients with head trauma, multiple traumas, cardiovascular disease, and hypotension not due to sepsis as it lowers intracranial pressure and has minimal effect on systemic blood pressure.
    Intravenous dosage
    Adults

    0.15 mg/kg/dose IV for unstable patients and 0.3 mg/kg/dose IV for stable patients has been recommended.

    Infants, Children, and Adolescents

    0.2 to 0.4 mg/kg/dose IV (Max: 20 mg/dose) over 30 to 60 seconds.

    For procedural sedation†.
    NOTE: Etomidate does not have analgesic properties; additional agents may be required for painful procedures.
    Intravenous dosage
    Adults

    0.1 to 0.3 mg/kg/dose IV (Max: 20 mg/dose) over 30 to 60 seconds.

    Children and Adolescents 10 to 17 years

    0.1 to 0.3 mg/kg/dose IV (Max: 20 mg/dose) over 30 to 60 seconds.

    For the acute treatment of severe hypercortisolism in patients with Cushing's syndrome† (Cushing's disease).
    Intravenous dosage
    Adults

    Common dose range per guidelines: 0.04 to 0.1 mg/kg/hour IV infusion for patients in an intensive care unit (ICU) who cannot take oral medications. A lower dose has been used for patients not in an ICU setting (i.e., 0.025 mg/kg/hour). Studies show approximately 100% serum cortisol control (10 to 20 mcg/dL). While higher doses (i.e., 0.5 to 1 mg/kg/hour) have been used in critical care settings, hydrocortisone must be used as add-back treatment to avoid etomidate-induced adrenal insufficiency.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    Specific maximum dosage information is not available. Dosage must be individualized.

    Geriatric

    Specific maximum dosage information is not available. Dosage must be individualized.

    Adolescents

    Specific maximum dosage information is not available. Dosage must be individualized. 0.4 mg/kg/dose IV (Max: 20 mg/dose) has been used off-label as a sedative during rapid-sequence intubation.

    Children

    10 to 12 years: Specific maximum dosage information is not available. Dosage must be individualized. 0.4 mg/kg/dose IV (Max: 20 mg/dose) has been used off-label as a sedative during rapid-sequence intubation.
    1 to 9 years: Safety and efficacy have not been established; however, 0.4 mg/kg/dose IV (Max: 20 mg/dose) has been used off-label as a sedative during rapid-sequence intubation.

    Infants

    Safety and efficacy have not been established; however, 0.4 mg/kg/dose IV (Max: 20 mg/dose) has been used off-label as a sedative during rapid-sequence intubation.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Although specific guidelines for dosage adjustments in hepatic impairment are not available, lower doses may be required in these patients, especially those with cirrhosis or esophageal varices.

    Renal Impairment

    Specific guidelines for dosage adjustments in patients with renal impairment are not available; however, lower doses may be required in these patients.

    ADMINISTRATION

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Etomidate injection is solely for intravenous administration and should only be given by individuals trained in the administration of general anesthetics. Dosage of etomidate must be individualized.
    Do not administer by prolonged infusion.

    STORAGE

    Amidate:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Sepsis, shock

    Do not use etomidate routinely in patients with evidence of septic shock or other sepsis-related organ dysfunction; adrenal suppression and higher mortality rates have been seen with etomidate use in this population.[52000] [63412] [64985] Etomidate is not intended for administration by prolonged infusion because of the risks of prolonged suppression of endogenous cortisol and aldosterone production. These reductions have not been associated with changes in vital signs or evidence of mortality; however, where concern exists for patients undergoing severe stress (e.g., those critically ill, including those with sepsis), exogenous cortisol replacement should be considered.

    Intraarterial administration

    Although tissue necrosis usually does not occur following inadvertent intra-arterial injection, intraarterial administration of etomidate is not recommended.

    Geriatric, hypertension

    Etomidate may induce cardiac depression in geriatric patients, especially those with hypertension. Due to age-related differences in pharmacokinetic parameters, elderly patients may require lower doses of etomidate than younger patients.

    Hypovolemia, trauma

    There are insufficient data concerning the use of etomidate in patients with recent severe trauma or hypovolemia to predict the cardiovascular response in these circumstances.

    Esophageal varices, hepatic disease

    Since etomidate is extensively metabolized by the liver, use caution when administering etomidate to patients with hepatic disease. These patients may require lower doses and may be at increased risk for adverse effects. Limited data suggest that the volume of distribution and elimination half-life of etomidate are approximately double in patients with cirrhosis or esophageal varices as compared to healthy subjects.

    Renal impairment

    The risk of adverse reactions to etomidate is increased in patients with renal impairment.

    Labor, obstetric delivery, pregnancy

    There are no adequate and well controlled studies during human pregnancy. Reduced pup survival was observed in pregnant rabbits intravenously administered etomidate 1.5 or 4.5 mg/kg/day (1.6 or 4.9 times the human induction dose of 0.3 mg/kg based on body surface area) during organogenesis. Increased still born fetuses and decreased pup survival were observed at all doses when pregnant rats received intravenous etomidate 0.31, 1.25, or 5 mg/kg/day (0.17, 0.68, or 2.7 times the human induction dose of 0.3 mg/kg based on body surface area) during gestation and throughout lactation. Repeated or lengthy use of general anesthetic and sedation drugs during surgeries or procedures during the third trimester of pregnancy may have negative effects on fetal brain development. Consider the benefits of appropriate anesthesia in pregnant women against the potential risks, especially for procedures that may last more than 3 hours or if multiple procedures are required prior to delivery. It may be appropriate to delay certain procedures if doing so will not jeopardize the health of the child and/or mother. No specific anesthetic or sedation drug has been shown to be safer than another. Human studies suggest that a single short exposure to a general anesthetic in young pediatric patients is unlikely to have negative effects on behavior and learning; however, further research is needed to fully characterize how anesthetic exposure affects brain development. Use during labor and obstetric delivery (including caesarean section) is not recommended because sufficient data are not available to support its use in this setting.

    Breast-feeding

    Use caution when administering etomidate to a breast-feeding woman. Twenty women undergoing Cesarean section received 0.3 mg/kg IV for induction of anesthesia. Maternal serum concentrations ranged from 340 to 2,500 ng/mL at 5 minutes after the dose, and serum concentrations were not detectable in any of the 2 hour samples. Mean colostrum concentrations were 79.3 ng/L (range 0 to 420 ng/L) at 30 minutes and 16.2 ng/L (range 0 to 60 ng/L) at 2 hours after the dose. Etomidate was not detected in any colostrum samples 4 hours after the dose. In general, the healthy term infant can safely nurse as soon after surgery as the mother is awake and alert.

    Children, infants, neonates

    Repeated or lengthy use of general anesthetic and sedation drugs during surgeries or procedures in neonates, infants, and children younger than 3 years, including in utero exposure during the third trimester, may have negative effects on brain development. Consider the benefits of appropriate anesthesia in young children against the potential risks, especially for procedures that may last more than 3 hours or if multiple procedures are required during the first 3 years of life. It may be appropriate to delay certain procedures if doing so will not jeopardize the health of the child. No specific anesthetic or sedation drug has been shown to be safer than another. Human studies suggest that a single short exposure to a general anesthetic in young pediatric patients is unlikely to have negative effects on behavior and learning; however, further research is needed to fully characterize how anesthetic exposure affects brain development.[61572]

    Driving or operating machinery

    Patients should be counseled not to attempt driving or operating machinery for at least 24 hours after receiving etomidate. Patients should have a caregiver present to drive them home after outpatient procedures where they received etomidate.

    ADVERSE REACTIONS

    Severe

    apnea / Delayed / Incidence not known
    laryngospasm / Rapid / Incidence not known
    bradycardia / Rapid / Incidence not known
    arrhythmia exacerbation / Early / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known

    Moderate

    myoclonia / Delayed / 74.0-74.0
    tachypnea / Early / Incidence not known
    respiratory depression / Rapid / Incidence not known
    hypoventilation / Rapid / Incidence not known
    hypertension / Early / Incidence not known
    hypotension / Rapid / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    adrenocortical insufficiency / Delayed / Incidence not known
    hypoaldosteronism / Delayed / Incidence not known

    Mild

    injection site reaction / Rapid / 1.2-42.0
    nausea / Early / Incidence not known
    vomiting / Early / Incidence not known
    hyperventilation / Early / Incidence not known
    hiccups / Early / Incidence not known

    DRUG INTERACTIONS

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

    PREGNANCY AND LACTATION

    Pregnancy

    Use caution when administering etomidate to a breast-feeding woman. Twenty women undergoing Cesarean section received 0.3 mg/kg IV for induction of anesthesia. Maternal serum concentrations ranged from 340 to 2,500 ng/mL at 5 minutes after the dose, and serum concentrations were not detectable in any of the 2 hour samples. Mean colostrum concentrations were 79.3 ng/L (range 0 to 420 ng/L) at 30 minutes and 16.2 ng/L (range 0 to 60 ng/L) at 2 hours after the dose. Etomidate was not detected in any colostrum samples 4 hours after the dose. In general, the healthy term infant can safely nurse as soon after surgery as the mother is awake and alert.

    MECHANISM OF ACTION

    Etomidate appears to facilitate GABAminergic neurotransmission by increasing the number of available GABA receptors, possibly by displacing endogenous inhibitors of GABA binding. Etomidate produces clinical responses such as hypnosis, elevations in arterial carbon dioxide tension, reduced cortisol plasma levels, and, similar to thiopental, a transient 20% to 30% decrease in cerebral blood flow. This reduction appears to be uniform in the absence of space-occupying lesions. Etomidate induction is usually followed by a moderate decrease of intracranial pressure, lasting for several minutes. Preliminary data suggest etomidate will lower intraocular pressure moderately. Also, based on animal studies, etomidate induces neocortical sleep. These studies suggest the effects of etomidate are at least partially due to depression of the brainstem reticular formation. Etomidate also inhibits steroidogenesis, which prevents its long-term use for ICU sedation. Inhibition is probably due to blockage of 11-beta-hydroxylation within the adrenal cortex. Reduced plasma cortisol and aldosterone levels appear to be unresponsive to ACTH stimulation.

    PHARMACOKINETICS

    Etomidate is administered intravenously. It is approximately 76% protein-bound. Etomidate is rapidly metabolized by ester hydrolysis in the liver. An inactive acid metabolite accounts for 80% of the urinary excretion. Approximately 75% of an administered dose is excreted in the urine during the first day after administration. Etomidate's half-life is approximately 75 minutes.
     
    Affected cytochrome P450 isoenzymes and drug transporters: none

    Intravenous Route

    The onset of action is 0.5 to 1 minute.[64934] After IV administration, the minimal hypnotic plasma concentration is 0.23 mcg/mL. The duration of etomidate-induced hypnosis is dose-dependent, usually lasting 3 to 5 minutes when an average dose (0.3 mg/kg) is used.[49500]