Ultane

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Ultane

Classes

Inhalation General Anesthetics

Administration
Inhalation Administration

Administration should only be conducted by individuals trained in the administration of general anesthetics.
No specific premedication is either indicated or contraindicated. The decision to premedicate and choice of medication is left to the discretion of the anesthesiologist.
As the level of anesthesia may be altered rapidly, only vaporizers producing predictable concentrations should be used. The concentration being delivered from a vaporizer should be known, which may be accomplished by use of vaporizer calibrated specifically for sevoflurane.
As with other inhalational anesthetics, degradation and production of degradation products can occur when sevoflurane is exposed to desiccated absorbents. An unusually delayed rise or unexpected decline of inspired sevoflurane concentration compared to the vaporizer setting may be associated with excessive heating of the CO2 absorbent and chemical breakdown of sevoflurane. Replace the CO2 absorbent if it is suspected that it may be desiccated. The exothermic reaction that occurs with sevoflurane and CO2 absorbents is increased when the CO2 absorbent becomes desiccated such as after an extended period of dry gas flow through the CO2 absorbent canisters. The color indicator of most CO2 absorbents may not change upon desiccation. Therefore, the lack of significant color change should not be taken as an assurance of adequate hydration. Replace CO2 absorbents routinely regardless of the state of the color indicator. Rare cases of extreme heat, smoke, and spontaneous fire in the anesthesia breathing circuit have been reported during sevoflurane use in conjunction with the use of desiccated CO2 absorbent, specifically those containing potassium hydroxide. Potassium hydroxide containing CO2 absorbents are not recommended for use with sevoflurane.
Concurrent administration of sevoflurane is compatible with the use of barbiturates, propofol, and other commonly used intravenous anesthetics.
The recovery from general anesthesia should be assessed carefully before a patient is discharged from the postanesthesia care unit.

Adverse Reactions
Severe

laryngospasm / Rapid / 2.0-8.0
bradycardia / Rapid / 5.0-5.0
apnea / Delayed / 0-2.0
bronchospasm / Rapid / 0-1.0
proteinuria / Delayed / 0-1.0
oliguria / Early / 0-1.0
hyperkalemia / Delayed / 0-1.0
myoglobinuria / Delayed / 0-1.0
AV block / Early / 0-1.0
atrial fibrillation / Early / 0-1.0
anaphylactoid reactions / Rapid / Incidence not known
angioedema / Rapid / Incidence not known
malignant hyperthermia / Rapid / Incidence not known
seizures / Delayed / Incidence not known
hepatic failure / Delayed / Incidence not known
hepatic necrosis / Delayed / Incidence not known
arrhythmia exacerbation / Early / Incidence not known
cardiac arrest / Early / Incidence not known
torsade de pointes / Rapid / Incidence not known
ventricular fibrillation / Early / Incidence not known
ventricular tachycardia / Early / Incidence not known

Moderate

hypotension / Rapid / 4.0-11.0
sinus tachycardia / Rapid / 2.0-6.0
hypertension / Early / 2.0-2.0
wheezing / Rapid / 0-1.0
hypertonia / Delayed / 0-1.0
confusion / Early / 0-1.0
glycosuria / Early / 0-1.0
urinary retention / Early / 0-1.0
elevated hepatic enzymes / Delayed / 0-1.0
hyperglycemia / Delayed / 0-1.0
hyperbilirubinemia / Delayed / 0-1.0
hypophosphatemia / Delayed / 0-1.0
ST-T wave changes / Rapid / 0-1.0
amblyopia / Delayed / 0-1.0
conjunctivitis / Delayed / 0-1.0
dyspnea / Early / 0-1.0
hypoventilation / Rapid / 0-1.0
hypoxia / Early / 0-1.0
thrombocytopenia / Delayed / 0-1.0
contact dermatitis / Delayed / Incidence not known
delirium / Early / Incidence not known
hepatitis / Delayed / Incidence not known
jaundice / Delayed / Incidence not known
QT prolongation / Rapid / Incidence not known
respiratory depression / Rapid / Incidence not known

Mild

nausea / Early / 25.0-25.0
vomiting / Early / 18.0-18.0
agitation / Early / 7.0-15.0
cough / Delayed / 5.0-11.0
shivering / Rapid / 6.0-6.0
dizziness / Early / 4.0-4.0
hypersalivation / Early / 2.0-4.0
pruritus / Rapid / 0-1.0
rash / Early / 0-1.0
insomnia / Early / 0-1.0
headache / Early / 1.0-1.0
syncope / Early / 0-1.0
hyperventilation / Early / 0-1.0
hiccups / Early / 0-1.0
pharyngitis / Delayed / 0-1.0
xerostomia / Early / 0-1.0
dysgeusia / Early / 0-1.0
fever / Early / 1.0-1.0
asthenia / Delayed / 0-1.0
hypothermia / Delayed / 1.0-1.0
leukocytosis / Delayed / 0-1.0
urticaria / Rapid / Incidence not known
restlessness / Early / Incidence not known
drowsiness / Early / Incidence not known

Common Brand Names

Ultane

Dea Class

Rx

Description

Halogenated general anesthetic; depth of anesthesia is easily adjusted; induction and recovery from anesthesia is rapid; cardiorespiratory depression is minimal; generally safe in patients with coronary artery disease; appropriate for pediatric patients

Dosage And Indications
For use in general anesthesia induction during inpatient or outpatient surgery.
NOTE: Sevoflurane has a nonpungent odor and does not cause respiratory irritability; it is suitable for mask induction in children and adults.
NOTE: Dosage of sevoflurane must be individualized based on patient response.
Inhalation dosage Adults

Using a vital capacity induction technique, inspired concentrations of 8% sevoflurane in combination with oxygen (1 L/minute) and nitrous oxide (2 L/minute) were used to obtain loss of consciousness followed by a 30 second IV injection of remifentanil (1 to 1.5 mcg/kg). Induction time was 3.4 +/- 2.2 minutes.

Children and Adolescents

Inspired concentrations of 8% or 12% sevoflurane in oxygen/nitrous oxide (1:1 ratio) at 6 L/minute total gas flow was administered after 15 seconds of nitrous oxide/oxygen (1:1 ratio) to patients 5 to 10 years of age. In another study of patients 5 to 15 years of age, induction was performed using a circle-absorber breathing circuit primed with sevoflurane 7% in 6 L/minute 50% nitrous oxide/oxygen fresh gas flow. The inspired sevoflurane concentration was reduced to 4% when the pupils were divergent and to 2% when the pupils were central. At this point, the fresh gas flow was reduced to 2 L/minute. The time to loss of the eyelash reflex was less than 1 minute.

For general anesthesia maintenance during inpatient or outpatient surgery.
NOTE: Sevoflurane can be administered with any type of anesthesia circuit. Determine the concentration of sevoflurane being delivered from a vaporizer during anesthesia. The administration of general anesthesia must be individualized based on the patient's response.
NOTE: No specific premedication is either indicated or contraindicated with sevoflurane. The decision as to whether or not to premedicate and the choice of premedication is left to the discretion of the anesthesiologist.
Inhalation dosage Adults

The usual maintenance dose is 0.5% to 3% with or without nitrous oxide to maintain surgical anesthesia.

Children and Adolescents

The usual maintenance dose is 0.5% to 3% with or without nitrous oxide to maintain surgical anesthesia.

Dosing Considerations
Hepatic Impairment

Sevoflurane can be administered to patients with mild-to-moderate hepatic impairment. However, sevoflurane has not been studied in patients with severe hepatic impairment.

Renal Impairment

Specific guidelines for dosage adjustments in renal impairment are not available. The safety of administering sevoflurane to patients with a serum creatinine > 1.5 mg/dl has not been established and cannot be recommended.

Drug Interactions

Abarelix: (Major) Since abarelix can cause QT prolongation, abarelix should be used cautiously, if at all, with other drugs that are associated with QT prolongation including sevoflurane.
Acetaminophen; Aspirin; Diphenhydramine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Acetaminophen; Caffeine; Dihydrocodeine: (Major) Concomitant use of dihydrocodeine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Acetaminophen; Caffeine; Pyrilamine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Acetaminophen; Chlorpheniramine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including phenylephrine, which can increase the risk of developing cardiac arrhythmias and hypotension. (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: (Major) Avoid administration of pseudoephedrine products to patients who have recently undergone, or will soon undergo, a procedure or treatment that requires general anesthesia. Specifically, halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including 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 : (Major) Halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including phenylephrine, which can increase the risk of developing cardiac arrhythmias and hypotension. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Acetaminophen; Codeine: (Major) Concomitant use of codeine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Acetaminophen; Dextromethorphan; Doxylamine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including phenylephrine, which can increase the risk of developing cardiac arrhythmias and hypotension.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Major) Avoid administration of pseudoephedrine products to patients who have recently undergone, or will soon undergo, a procedure or treatment that requires general anesthesia. Specifically, halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including pseudoephedrine.
Acetaminophen; Dextromethorphan; Phenylephrine: (Major) Halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including phenylephrine, which can increase the risk of developing cardiac arrhythmias and hypotension.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Major) Avoid administration of pseudoephedrine products to patients who have recently undergone, or will soon undergo, a procedure or treatment that requires general anesthesia. Specifically, halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including pseudoephedrine.
Acetaminophen; Diphenhydramine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Acetaminophen; Guaifenesin; Phenylephrine: (Major) Halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including phenylephrine, which can increase the risk of developing cardiac arrhythmias and hypotension.
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; Phenylephrine: (Major) Halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including phenylephrine, which can increase the risk of developing cardiac arrhythmias and hypotension.
Acetaminophen; Pseudoephedrine: (Major) Avoid administration of pseudoephedrine products to patients who have recently undergone, or will soon undergo, a procedure or treatment that requires general anesthesia. Specifically, halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including pseudoephedrine.
Acrivastine; Pseudoephedrine: (Major) Avoid administration of pseudoephedrine products to patients who have recently undergone, or will soon undergo, a procedure or treatment that requires general anesthesia. Specifically, halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including pseudoephedrine. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Adagrasib: (Major) Concomitant use of adagrasib and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Alfentanil: (Moderate) Concurrent use of sevoflurane with opiate agonists such as alfentanil can reduce the minimal alveolar concentration (MAC) and increase the CNS depression, hypotension, and respiratory depression associated with sevoflurane administration. Postoperative respiratory depression associated with alfentanil may also be augmented. If alfentanil is used with one of these drugs, the dose of one or both agents may need to be reduced. Requirements for volatile inhalation anesthetics or alfentanil infusion are reduced by 30% to 50% for the first hour of maintenance following an anesthetic induction dose of alfentanil. Discontinue alfentanil infusions at least 10 to 15 minutes before the end of surgery during general anesthesia.
Alfuzosin: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with alfuzosin. Halogenated anesthetics can prolong the QT interval. Based on electrophysiology studies performed by the manufacturer, alfuzosin has a slight effect to prolong the QT interval. The QT prolongation appeared less with alfuzosin 10 mg than with 40 mg. The manufacturer warns that the QT effect of alfuzosin should be considered prior to administering the drug to patients taking other medications known to prolong the QT interval.
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; 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.
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. Close perioperative monitoring is recommended in patients undergoing general anesthesia who are on amiodarone therapy as they may be more sensitive to the myocardial depressant and conduction effects of halogenated anesthetics, which may include QT prolongation. Due to the extremely long half-life of amiodarone, a drug interaction is also possible for days to weeks after discontinuation of amiodarone.
Amisulpride: (Major) Monitor ECGs for QT prolongation when amisulpride is administered with halogenated anesthetics. Amisulpride causes dose- and concentration- dependent QT prolongation. Halogenated anesthetics can prolong the QT interval.
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.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with clarithromycin. Halogenated anesthetics can prolong the QT interval and clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP).
Amphetamine; Dextroamphetamine Salts: (Major) Inhalational general anesthetics (e.g., enflurane, halothane, isoflurane, and methoxyflurane) may sensitize the myocardium to the effects of stimulants. Dosages of the amphetamines should be substantially reduced prior to surgery, and caution should be observed with concurrent use of anesthetics.
Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported during post-marketing use of anagrelide. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with anagrelide include halogenated 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: (Major) Use apomorphine and halogenated anesthetics together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Halogenated anesthetics can prolong the QT interval. In addition, concomitant administration of apomorphine and halogenated anesthetics could also 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.
Aripiprazole: (Major) Concomitant use of aripiprazole and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Arsenic Trioxide: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with arsenic trioxide. Halogenated anesthetics can prolong the QT interval. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported.
Artemether; Lumefantrine: (Major) Halogenated anesthetics should be avoided with artemether; lumefantrine. Halogenated anesthetics can prolong the QT interval. The administration of artemether; lumefantrine is associated with prolongation of the QT interval. Although there are no studies examining the effects of artemether; lumefantrine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation and should be avoided. Consider ECG monitoring if halogenated anesthetics must be used with or after artemether; lumefantrine treatment.
Articaine; Epinephrine: (Moderate) Monitor patients who are concomitantly receiving epinephrine and sevoflurane for the development of arrhythmias. Halogenated anesthetics, such as sevoflurane, sensitize the myocardium and may potentiate the arrhythmogenic effects of epinephrine. If occur, such arrhythmias may respond to beta-blocker administration. A study investigating the epinephrine induced arrhythmogenic effect of sevoflurane in adult patients undergoing transsphenoidal hypophysectomy demonstrated that the threshold dose of epinephrine (i.e., the dose at which the first sign of arrhythmia was observed) producing multiple ventricular arrhythmias was 5 mcg/kg.
Asenapine: (Major) Asenapine has been associated with QT prolongation. According to the manufacturer, asenapine should not be used with other agents also known to have this effect (e.g., halogenated anesthetics). Halogenated anesthetics can prolong the QT interval.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) General anesthetics potentiate the effects of other CNS depressants, including skeletal muscle relaxants.
Aspirin, ASA; Carisoprodol: (Moderate) General anesthetics potentiate the effect of other CNS depressants including carisoprodol.
Aspirin, ASA; Carisoprodol; Codeine: (Major) Concomitant use of codeine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. (Moderate) General anesthetics potentiate the effect of other CNS depressants including carisoprodol.
Aspirin, ASA; Oxycodone: (Major) Concomitant use of oxycodone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Atomoxetine: (Major) Concomitant use of atomoxetine and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Atracurium: (Moderate) Reduce the initial atracurium dose by approximately one-third (i.e., to 0.25 to 0.35 mg/kg) to adjust for the potentiating effects of sevoflurane if atracurium is first administered under steady-state of sevoflurane. Recommended initial doses of atracurium may be used to facilitate tracheal intubation before administration of sevoflurane.
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.
Azithromycin: (Major) Avoid coadministration of azithromycin with halogenated anesthetics due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Halogenated anesthetics can prolong the QT interval.
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.
Bedaquiline: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering bedaquiline with halogenated anesthetics. Both bedaquiline and halogenated anesthetics have been reported to prolong the QT interval. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy.
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.
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.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Brompheniramine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Brompheniramine; Dextromethorphan; Phenylephrine: (Major) Halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including phenylephrine, which can increase the risk of developing cardiac arrhythmias and hypotension. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Brompheniramine; Phenylephrine: (Major) Halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including phenylephrine, which can increase the risk of developing cardiac arrhythmias and hypotension. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Brompheniramine; Pseudoephedrine: (Major) Avoid administration of pseudoephedrine products to patients who have recently undergone, or will soon undergo, a procedure or treatment that requires general anesthesia. Specifically, halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including 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: (Major) Avoid administration of pseudoephedrine products to patients who have recently undergone, or will soon undergo, a procedure or treatment that requires general anesthesia. Specifically, halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including pseudoephedrine. (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) If epinephrine is added to bupivacaine, do not use the mixture in a patient during or following treatment with general anesthetics. Concurrent use has been associated with the development of cardiac arrhythmias, and should be avoided, if possible. (Moderate) Monitor patients who are concomitantly receiving epinephrine and sevoflurane for the development of arrhythmias. Halogenated anesthetics, such as sevoflurane, sensitize the myocardium and may potentiate the arrhythmogenic effects of epinephrine. If occur, such arrhythmias may respond to beta-blocker administration. A study investigating the epinephrine induced arrhythmogenic effect of sevoflurane in adult patients undergoing transsphenoidal hypophysectomy demonstrated that the threshold dose of epinephrine (i.e., the dose at which the first sign of arrhythmia was observed) producing multiple ventricular arrhythmias was 5 mcg/kg.
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) Due to the potential for QT prolongation and additive CNS depressant effects, cautious use and close monitoring are advisable if concurrent use of halogenated anesthetics and buprenorphine is necessary. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Halogenated anesthetics have a possible risk for QT prolongation and TdP. FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. In addition, during co-administration of buprenorphine with other CNS depressants, hypotension, profound sedation, coma, respiratory depression, or death may occur. 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. The buprenorphine dose may also need to be lowered when given with drugs that reduce hepatic blood flow, such as halothane, which causes a reduction in hepatic blood flow by about 30%.
Buprenorphine; Naloxone: (Major) Due to the potential for QT prolongation and additive CNS depressant effects, cautious use and close monitoring are advisable if concurrent use of halogenated anesthetics and buprenorphine is necessary. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Halogenated anesthetics have a possible risk for QT prolongation and TdP. FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. In addition, during co-administration of buprenorphine with other CNS depressants, hypotension, profound sedation, coma, respiratory depression, or death may occur. 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. The buprenorphine dose may also need to be lowered when given with drugs that reduce hepatic blood flow, such as halothane, which causes a reduction in hepatic blood flow by about 30%.
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.
Butalbital; Aspirin; 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.
Cabotegravir; Rilpivirine: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with rilpivirine. Halogenated anesthetics can prolong the QT interval. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval.
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 halogenated anesthetics. 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.
Carbamazepine: (Moderate) Caution is advised with the concomitant use of sevoflurane and carbamazepine as concurrent use may increase the risk of hepatotoxicity.
Carbidopa; Levodopa: (Major) If administered before halogenated anesthetics, levodopa without a concurrent decarboxylase inhibitor has been associated with cardiac arrhythmias. This interaction is presumably due to the levodopa-induced increases in plasma dopamine. Levodopa single-agent therapy should be discontinued 6 to 8 hours before administering halogenated anesthetics. Otherwise, when general anesthesia is required, levodopa may be continued as long as the patient is permitted to take oral medication. Patients should be observed for signs of neuroleptic malignant syndrome while therapy is interrupted, and the usual levodopa regimen should be administered as soon as the patient is able to take oral medication.
Carbidopa; Levodopa; Entacapone: (Major) If administered before halogenated anesthetics, levodopa without a concurrent decarboxylase inhibitor has been associated with cardiac arrhythmias. This interaction is presumably due to the levodopa-induced increases in plasma dopamine. Levodopa single-agent therapy should be discontinued 6 to 8 hours before administering halogenated anesthetics. Otherwise, when general anesthesia is required, levodopa may be continued as long as the patient is permitted to take oral medication. Patients should be observed for signs of neuroleptic malignant syndrome while therapy is interrupted, and the usual levodopa regimen should be administered as soon as the patient is able to take oral medication.
Carbinoxamine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
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.
Ceritinib: (Major) Avoid coadministration of ceritinib with halogenated anesthetics if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Halogenated anesthetics can also prolong the QT interval.
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: (Major) Avoid administration of pseudoephedrine products to patients who have recently undergone, or will soon undergo, a procedure or treatment that requires general anesthesia. Specifically, halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including 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; Dexchlorpheniramine; Pseudoephedrine: (Major) Avoid administration of pseudoephedrine products to patients who have recently undergone, or will soon undergo, a procedure or treatment that requires general anesthesia. Specifically, halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including 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.
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.
Chloroquine: (Major) Avoid coadministration of chloroquine with halogenated anesthetics due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Halogenated anesthetics are known to prolong the QT interval.
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: (Major) Halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including phenylephrine, which can increase the risk of developing cardiac arrhythmias and hypotension. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Avoid administration of pseudoephedrine products to patients who have recently undergone, or will soon undergo, a procedure or treatment that requires general anesthesia. Specifically, halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including 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. (Major) Halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including phenylephrine, which can increase the risk of developing cardiac arrhythmias and hypotension. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Chlorpheniramine; Hydrocodone: (Major) Concomitant use of hydrocodone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Avoid administration of pseudoephedrine products to patients who have recently undergone, or will soon undergo, a procedure or treatment that requires general anesthesia. Specifically, halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including pseudoephedrine. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Chlorpheniramine; Phenylephrine: (Major) Halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including phenylephrine, which can increase the risk of developing cardiac arrhythmias and hypotension. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Chlorpheniramine; Pseudoephedrine: (Major) Avoid administration of pseudoephedrine products to patients who have recently undergone, or will soon undergo, a procedure or treatment that requires general anesthesia. Specifically, halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including pseudoephedrine. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Chlorpromazine: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with chlorpromazine. Halogenated anesthetics can prolong the QT interval. Phenothiazines have been associated with a risk of QT prolongation and/or torsade de pointes (TdP). This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Agents that prolong the QT interval could lead to torsade de pointes when combined with a phenothiazine, and therefore are generally not recommended for combined use. In addition, phenothiazines can potentiate the CNS-depressant action of anesthetics.
Chlorzoxazone: (Moderate) General anesthetics potentiate the effects of other CNS depressants, including skeletal muscle relaxants.
Ciprofloxacin: (Major) Concomitant use of ciprofloxacin and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Cisapride: (Contraindicated) QT prolongation and ventricular arrhythmias, including torsade de pointes (TdP) and death, have been reported with cisapride. Because of the potential for TdP, use of the halogenated anesthetics with cisapride is contraindicated.
Cisatracurium: (Moderate) Consider administering less frequent or lower cisatracurium maintenance bolus doses for long surgical procedures using sevoflurane administered with nitrous oxide/oxygen at the 1.25 MAC level for at least 30 minutes. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration. Concomitant use of cisatracurium and sevoflurane may prolong neuromuscular blockade. No adjustment to the initial cisatracurium maintenance bolus dose should be necessary when cisatracurium is administered shortly after initiation of sevoflurane.
Citalopram: (Major) Concomitant use of halogenated anesthetics and citalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Clarithromycin: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with clarithromycin. Halogenated anesthetics can prolong the QT interval and clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP).
Class IA Antiarrhythmics: (Major) Halogenated anesthetics should be used cautiously with class IA antiarrhythmics (disopyramide, procainamide, quinidine). Halogenated anesthetics can prolong the QT interval and class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP).
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.
Clofazimine: (Major) Concomitant use of clofazimine and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Clozapine: (Major) Concomitant use of clozapine and halogenated anesthetics increases the risk of QT/QTc prolongation, torsade de pointes (TdP), excessive sedation and respiratory depression, and neuroleptic malignant syndrome (NMS). Avoid concomitant use if possible, especially in patients with additional risk factors for these adverse effects. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary and monitor for signs and symptoms of NMS and prolonged sedation and respiratory depression.
Cocaine: (Major) Halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including cocaine. The combination may also result in an increased risk of QT prolongation.
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) Avoid administration of pseudoephedrine products to patients who have recently undergone, or will soon undergo, a procedure or treatment that requires general anesthesia. Specifically, halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including 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. (Major) Halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including phenylephrine, which can increase the risk of developing cardiac arrhythmias and hypotension. (Moderate) Halogenated anesthetics carry a possible risk for QT prolongation and torsade de pointes (TdP). Promethazine carries a possible risk of QT prolongation and should be used cautiously with these anesthetics, with proper blood pressure and heart rate monitoring.
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. (Moderate) Halogenated anesthetics carry a possible risk for QT prolongation and torsade de pointes (TdP). Promethazine carries a possible risk of QT prolongation and should be used cautiously with these anesthetics, with proper blood pressure and heart rate monitoring.
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.
Crizotinib: (Major) Avoid coadministration of crizotinib with halogenated anesthetics due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Halogenated anesthetics can also prolong the QT interval.
Cyclizine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Cyproheptadine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Dantrolene: (Moderate) General anesthetics potentiate the effects of other CNS depressants, including skeletal muscle relaxants.
Dasatinib: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with dasatinib. Halogenated anesthetics can prolong the QT interval. In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval). Cautious dasatinib administration is recommended to patients who have or may develop QT prolongation such as patients taking drugs that lead to QT prolongation.
Degarelix: (Major) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents like halogenated anesthetics. Androgen deprivation therapy (i.e., degarelix) may prolong the QT/QTc interval. Halogenated anesthetics can also prolong the QT interval.
Desloratadine; Pseudoephedrine: (Major) Avoid administration of pseudoephedrine products to patients who have recently undergone, or will soon undergo, a procedure or treatment that requires general anesthesia. Specifically, halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including pseudoephedrine.
Deutetrabenazine: (Major) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and halogenated anesthetics. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range. Halogenated anesthetics can prolong the QT interval.
Dexbrompheniramine; Pseudoephedrine: (Major) Avoid administration of pseudoephedrine products to patients who have recently undergone, or will soon undergo, a procedure or treatment that requires general anesthesia. Specifically, halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including pseudoephedrine.
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: (Major) Avoid administration of pseudoephedrine products to patients who have recently undergone, or will soon undergo, a procedure or treatment that requires general anesthesia. Specifically, halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including pseudoephedrine. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Dexmedetomidine: (Major) Concomitant use of dexmedetomidine and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. In addition, consider a dosage reduction for dexmedetomidine or the anesthetic during concomitant use due to the risk of additive CNS effects.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Major) Halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including phenylephrine, which can increase the risk of developing cardiac arrhythmias and hypotension. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including phenylephrine, which can increase the risk of developing cardiac arrhythmias and hypotension.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Major) Avoid administration of pseudoephedrine products to patients who have recently undergone, or will soon undergo, a procedure or treatment that requires general anesthesia. Specifically, halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including pseudoephedrine.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
Dimenhydrinate: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Diphenhydramine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Diphenhydramine; Ibuprofen: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Diphenhydramine; Naproxen:

ng> (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Diphenhydramine; Phenylephrine: (Major) Halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including phenylephrine, which can increase the risk of developing cardiac arrhythmias and hypotension. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Disulfiram: (Moderate) Disulfiram decreases the activity of cytochrome P450 2E1 isoenzyme and may inhibit sevoflurane metabolism.
Dofetilide: (Major) Coadministration of dofetilide and halogenated anesthetics is not recommended as concurrent use may increase the risk of QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Halogenated anesthetics can prolong the QT interval.
Dolasetron: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with dolasetron. Halogenated anesthetics can prolong the QT interval. Dolasetron has been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Use of dolasetron injection for the prevention of chemotherapy-induced nausea and vomiting is contraindicated because the risk of QT prolongation is higher with the doses required for this indication; when the injection is used at lower doses (i.e., those approved for post-operative nausea and vomiting) or when the oral formulation is used, the risk of QT prolongation is lower and caution is advised.
Dolutegravir; Rilpivirine: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with rilpivirine. Halogenated anesthetics can prolong the QT interval. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval.
Donepezil: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include halogenated anesthetics. In addition, Muscle relaxation produced by succinylcholine can be prolonged when the drug is administered with a cholinesterase inhibitor, like donepezil. If used during surgery, extended respiratory depression could result from prolonged neuromuscular blockade. Other neuromuscular blockers may interact with donepezil in a similar fashion. Cholinesterase inhibitors are therefore also likely to exaggerate muscle relaxation under general anesthetics.
Donepezil; Memantine: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include halogenated anesthetics. In addition, Muscle relaxation produced by succinylcholine can be prolonged when the drug is administered with a cholinesterase inhibitor, like donepezil. If used during surgery, extended respiratory depression could result from prolonged neuromuscular blockade. Other neuromuscular blockers may interact with donepezil in a similar fashion. Cholinesterase inhibitors are therefore also likely to exaggerate muscle relaxation under general anesthetics.
Doxapram: (Major) Halogenated anesthetics sensitize the myocardium to sympathomimetics, like doxapram. Delay doxapram administration until the halogenated anesthetic is excreted to lessen risk for arrhythmias, including ventricular tachycardia and ventricular fibrillation.
Doxazosin: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
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.
Dronedarone: (Contraindicated) Concurrent use of halogenated anesthetics and dronedarone is contraindicated. Halogenated anesthetics prolong the QT interval. Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
Droperidol: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with droperidol. Halogenated anesthetics can prolong the QT interval. Droperidol should be administered with extreme caution to patients receiving other agents that may prolong the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsades de pointes (TdP). In December 2001, the FDA issued a black box warning regarding the use of droperidol and its association with QT prolongation and potential for cardiac arrhythmias based on post-marketing surveillance data. According to the revised 2001 labeling for droperidol, any drug known to have potential to prolong the QT interval should not be coadministered with droperidol.
Efavirenz: (Major) Although data are limited, coadministration of efavirenz and halogenated anesthetics may increase the risk for QT prolongation and torsade de pointes (TdP). Both drugs can prolong the QT interval.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Although data are limited, coadministration of efavirenz and halogenated anesthetics may increase the risk for QT prolongation and torsade de pointes (TdP). Both drugs can prolong the QT interval.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Although data are limited, coadministration of efavirenz and halogenated anesthetics may increase the risk for QT prolongation and torsade de pointes (TdP). Both drugs can prolong the QT interval.
Eliglustat: (Major) Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with eliglustat include halogenated anesthetics.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with rilpivirine. Halogenated anesthetics can prolong the QT interval. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with rilpivirine. Halogenated anesthetics can prolong the QT interval. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval.
Encorafenib: (Major) Avoid coadministration of encorafenib and halogenated anesthetics due to QT prolongation. If concurrent use cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib is associated with dose-dependent prolongation of the QT interval. Halogenated anesthetics can also prolong the QT interval.
Entrectinib: (Major) Avoid coadministration of entrectinib with halogenated anesthetics due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Halogenated anesthetics can prolong the QT interval.
Epinephrine: (Moderate) Monitor patients who are concomitantly receiving epinephrine and sevoflurane for the development of arrhythmias. Halogenated anesthetics, such as sevoflurane, sensitize the myocardium and may potentiate the arrhythmogenic effects of epinephrine. If occur, such arrhythmias may respond to beta-blocker administration. A study investigating the epinephrine induced arrhythmogenic effect of sevoflurane in adult patients undergoing transsphenoidal hypophysectomy demonstrated that the threshold dose of epinephrine (i.e., the dose at which the first sign of arrhythmia was observed) producing multiple ventricular arrhythmias was 5 mcg/kg.
Eplerenone: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Epoprostenol: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Eribulin: (Major) Eribulin and halogenated anesthetics have been associated with QT prolongation. If eribulin must be coadministered with a halogenated anesthetic, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
Erythromycin: (Major) Concomitant use of erythromycin and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Escitalopram: (Major) Concomitant use of escitalopram and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Esketamine: (Major) Although CNS depression is a desired effect of general anesthetics, patients also receiving esketamine should be closely monitored for additive effects that may prolong recovery after administration of a general anesthetic. If possible, avoid scheduling a treatment session with esketamine on the same day that general anesthesia is required. Patients who have received a dose of esketamine should be instructed not to drive or engage in other activities requiring complete mental alertness until the next day after a restful sleep.
Eszopiclone: (Moderate) A temporary dose reduction of eszopiclone should be considered following administration of general anesthetics. The risk of next-day psychomotor impairment is increased during co-administration of eszopiclone and other CNS depressants, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
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.
Fexofenadine; Pseudoephedrine: (Major) Avoid administration of pseudoephedrine products to patients who have recently undergone, or will soon undergo, a procedure or treatment that requires general anesthesia. Specifically, halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including pseudoephedrine.
Fingolimod: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with fingolimod. Halogenated anesthetics can prolong the QT interval. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. After the first fingolimod dose, overnight monitoring with continuous ECG in a medical facility is advised for patients taking QT prolonging drugs with a known risk of torsades de pointes (TdP). Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia.
Flecainide: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with flecainide. Halogenated anesthetics can prolong the QT interval. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsades de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Fluconazole: (Major) Concomitant use of fluconazole and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fluoxetine: (Major) Concomitant use of halogenated anesthetics and fluoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fluphenazine: (Minor) Halogenated anesthetics should be used cautiously and with close monitoring with fluphenazine. Halogenated anesthetics can prolong the QT interval and fluphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. In addition, phenothiazines can potentiate the CNS-depressant action of general anesthetics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Fluvoxamine: (Major) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of fluvoxamine and halogenated anesthetics. Halogenated anesthetics can prolong the QT interval. Reports of QT prolongation, associated with TdP (in exceptional cases, fatal), have been received. QT prolongation and TdP have been reported during postmarketing use of fluvoxamine.
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.
Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as halogenated anesthetics. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Halogenated anesthetics can also prolong the QT interval. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
Fosphenytoin: (Moderate) Caution is advised with the concomitant use of sevoflurane and fosphenytoin as concurrent use may increase the risk of hepatotoxicity.
Fostemsavir: (Major) Use halogenated anesthetics and fostemsavir together with caution. Halogenated anesthetics can prolong the QT interval. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, 4 times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
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.
Galantamine: (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.
Gemifloxacin: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with gemifloxacin. Halogenated anesthetics can prolong the QT interval. Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5-10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
Gemtuzumab Ozogamicin: (Major) Use gemtuzumab ozogamicin and halogenated anesthetics together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Halogenated anesthetics can prolong the QT interval.
Gentamicin: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving gentamicin.
Gilteritinib: (Major) Use caution and monitor for evidence of QT prolongation if concurrent use of gilteritinib and halogenated anesthetics is necessary. Both gilteritinib and halogenated anesthetics have been associated with QT prolongation; coadministration has the potential for additive effects.
Glasdegib: (Major) Avoid coadministration of glasdegib with halogenated anesthetics due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Halogenated anesthetics can also prolong the QT interval.
Goserelin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., goserelin) outweigh the potential risks of QT prolongation in patients receiving halogenated anesthetics. Androgen deprivation therapy may prolong the QT/QTc interval. Halogenated anesthetics can also prolong the QT interval.
Granisetron: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with granisetron. Halogenated anesthetics can prolong the QT interval. Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron in patients concurrently treated with drugs known to prolong the QT interval and/or are arrhythmogenic, may result in clinical consequences.
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; Phenylephrine: (Major) Halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including phenylephrine, which can increase the risk of developing cardiac arrhythmias and hypotension.
Guaifenesin; Pseudoephedrine: (Major) Avoid administration of pseudoephedrine products to patients who have recently undergone, or will soon undergo, a procedure or treatment that requires general anesthesia. Specifically, halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including pseudoephedrine.
Haloperidol: (Major) QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. According to the manufacturer of haloperidol, caution is advisable when prescribing the drug concurrently with medications known to prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with haloperidol include halogenated anesthetics.
Histrelin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving halogenated anesthetics. Androgen deprivation therapy may prolong the QT/QTc interval. Halogenated anesthetics can also prolong the QT interval.
Homatropine; Hydrocodone: (Major) Concomitant use of hydrocodone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Hydrocodone: (Major) Concomitant use of hydrocodone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Hydrocodone; Ibuprofen: (Major) Concomitant use of hydrocodone with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Avoid prescribing opioid cough medications in patients receiving a general anesthetic. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Hydrocodone; Pseudoephedrine: (Major) Avoid administration of pseudoephedrine products to patients who have recently undergone, or will soon undergo, a procedure or treatment that requires general anesthesia. Specifically, halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including 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.
Hydroxychloroquine: (Major) Concomitant use of hydroxychloroquine and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Hydroxyzine: (Major) Caution is recommended if hydroxyzine is administered with halogenated anesthetics due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, because hydroxyzine causes pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including halogenated anesthetics. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Halogenated anesthetics can prolong the QT interval.
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.
Ibuprofen; Pseudoephedrine: (Major) Avoid administration of pseudoephedrine products to patients who have recently undergone, or will soon undergo, a procedure or treatment that requires general anesthesia. Specifically, halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including pseudoephedrine.
Ibutilide: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Halogenated anesthetics can prolong the QT interval and should be used cautiously with ibutilide.
Iloperidone: (Major) Iloperidone has been associated with QT prolongation; however, torsade de pointes (TdP) has not been reported. According to the manufacturer, since iloperidone may prolong the QT interval, it should be avoided in combination with halogenated anesthetics which canalso prolong the QT interval.
Iloprost: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with halogenated anesthetics due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, monitor the ECG and electrolytes. Inotuzumab has been associated with QT interval prolongation. Halogenated anesthetics can also prolong the QT interval.
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.
Isoniazid, INH: (Major) Anesthetic requirements may be increased for sevoflurane with concomitant use of isoniazid, INH. The cytochrome P450 (CYP) 2E1 isoenzyme appears to be a predominant enzyme responsible for human oxidative sevoflurane metabolism. Isoniazid, INH has been shown to induce CYP2E1. Additionally, the concurrent use of sevoflurane and isoniazid may increase the risk of hepatotoxicity.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Anesthetic requirements may be increased for sevoflurane with concomitant use of isoniazid, INH. The cytochrome P450 (CYP) 2E1 isoenzyme appears to be a predominant enzyme responsible for human oxidative sevoflurane metabolism. Isoniazid, INH has been shown to induce CYP2E1. Additionally, the concurrent use of sevoflurane and isoniazid may increase the risk of hepatotoxicity. (Moderate) Caution is advised with the concomitant use of sevoflurane and rifampin as concurrent use may increase the risk of hepatotoxicity.
Isoniazid, INH; Rifampin: (Major) Anesthetic requirements may be increased for sevoflurane with concomitant use of isoniazid, INH. The cytochrome P450 (CYP) 2E1 isoenzyme appears to be a predominant enzyme responsible for human oxidative sevoflurane metabolism. Isoniazid, INH has been shown to induce CYP2E1. Additionally, the concurrent use of sevoflurane and isoniazid may increase the risk of hepatotoxicity. (Moderate) Caution is advised with the concomitant use of sevoflurane and rifampin as concurrent use may increase the risk of hepatotoxicity.
Isoproterenol: (Major) Avoid concomitant use of isoproterenol and halogenated anesthetics due to potential to sensitize the myocardium to the effects of sympathomimetic amines.
Itraconazole: (Major) Itraconazole has been associated with prolongation of the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with itraconazole include halogenated anesthetics.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with halogenated anesthetics due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Halogenated anesthetics can prolong the QT interval.
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and halogenated anesthetics due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with clarithromycin. Halogenated anesthetics can prolong the QT interval and clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP).
Lapatinib: (Major) Monitor ECGs for QT prolongation and monitor electrolytes if coadministration of lapatinib with halogenated anesthetics is necessary; correct electrolyte abnormalities prior to treatment. Halogenated anesthetics can prolong the QT interval. Lapatinib has also been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib.
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.
Lefamulin: (Major) Avoid coadministration of lefamulin with halogenated anesthetics as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, monitor ECG during treatment. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Halogenated anesthetics can prolong the QT interval.
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.
Lenvatinib: (Major) Avoid coadministration of lenvatinib with halogenated anesthetics due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Halogenated anesthetics can also prolong the QT interval.
Leuprolide: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving halogenated anesthetics. Androgen deprivation therapy may prolong the QT/QTc interval. Halogenated anesthetics can also prolong the QT interval.
Leuprolide; Norethindrone: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving halogenated anesthetics. Androgen deprivation therapy may prolong the QT/QTc interval. Halogenated anesthetics can also prolong the QT interval.
Levocetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with general anesthetics should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. CNS depression is a desired effect of general anesthetics; however, concurrent use with a CNS depressant may prolong recovery. If concurrent use is necessary, monitor patients closely.
Levodopa: (Major) If administered before halogenated anesthetics, levodopa without a concurrent decarboxylase inhibitor has been associated with cardiac arrhythmias. This interaction is presumably due to the levodopa-induced increases in plasma dopamine. Levodopa single-agent therapy should be discontinued 6 to 8 hours before administering halogenated anesthetics. Otherwise, when general anesthesia is required, levodopa may be continued as long as the patient is permitted to take oral medication. Patients should be observed for signs of neuroleptic malignant syndrome while therapy is interrupted, and the usual levodopa regimen should be administered as soon as the patient is able to take oral medication.
Levofloxacin: (Major) Concomitant use of levofloxacin and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and halogenated anesthetics due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
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: (Moderate) Monitor patients who are concomitantly receiving epinephrine and sevoflurane for the development of arrhythmias. Halogenated anesthetics, such as sevoflurane, sensitize the myocardium and may potentiate the arrhythmogenic effects of epinephrine. If occur, such arrhythmias may respond to beta-blocker administration. A study investigating the epinephrine induced arrhythmogenic effect of sevoflurane in adult patients undergoing transsphenoidal hypophysectomy demonstrated that the threshold dose of epinephrine (i.e., the dose at which the first sign of arrhythmia was observed) producing multiple ventricular arrhythmias was 5 mcg/kg.
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.
Lincosamides: (Moderate) Concurrent use of sevoflurane with systemic clindamycin can result in an additive neuromuscular blockade.
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.
Lithium: (Major) Concomitant use of lithium and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Lofexidine: (Major) Monitor ECG if lofexidine is coadministered with halogenated anesthetics due to the potential for additive QT prolongation. Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of torsade de pointes. Halogenated anesthetics can prolong the QT interval. Additionally, monitor for excessive hypotension and sedation during coadministration as lofexidine can potentiate the effects of CNS depressants.
Loop diuretics: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Loperamide: (Major) At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Drugs with a possible risk for QT prolongation and TdP, like halogenated anesthetics, should be used cautiously and with close monitoring with loperamide.
Loperamide; Simethicone: (Major) At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Drugs with a possible risk for QT prolongation and TdP, like halogenated anesthetics, should be used cautiously and with close monitoring with loperamide.
Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with halogenated anesthetics due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Lopinavir and halogenated anesthetics can both prolong the QT interval.
Loratadine; Pseudoephedrine: (Major) Avoid administration of pseudoephedrine products to patients who have recently undergone, or will soon undergo, a procedure or treatment that requires general anesthesia. Specifically, halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including pseudoephedrine.
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.
Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as halogenated anesthetics. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Halogenated anesthetics can prolong the QT interval.
Maprotiline: (Major) Halogenated anesthetics can prolong the QT interval. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with halogenated anesthetics include 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.
Mefloquine: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with mefloquine. Halogenated anesthetics can prolong the QT interval. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
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.
Meprobamate: (Moderate) The effects of CNS depressant drugs, such as meprobamate, may increase when administered concurrently with general anesthetics. A temporary dose reduction of meprobamate should be considered following administration of general anesthetics. The risk of next-day psychomotor impairment is increased during co-administration, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
Metaxalone: (Moderate) General anesthetics potentiate the effects of other CNS depressants, including skeletal muscle relaxants.
Methadone: (Major) The need to coadminister methadone with drugs known to prolong the QT interval should be done with extreme caution and a careful assessment of treatment risks versus benefits. Halogenated anesthetics can prolong the QT interval. Methadone is considered to be associated with an increased risk for QT prolongation and torsades de pointes (TdP), especially at higher doses (> 200 mg/day but averaging approximately 400 mg/day in adult patients). Laboratory studies, both in vivo and in vitro, have demonstrated that methadone inhibits cardiac potassium channels and prolongs the QT interval. Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction.
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.
Methylphenidate Derivatives: (Major) Avoid the use of methylphenidate or its derivatives in patients being treated with halogenated anesthetics (e.g., enflurane, halothane, isoflurane, and methoxyflurane) on the day of surgery. The use of Metadate CD is contraindicated on the day of surgery. Halogenated anesthetics may sensitize the cardiovascular system to the effects of methylphenidate increasing the risk of sudden blood pressure and heart rate increase during surgery.
Metronidazole: (Major) Concomitant use of metronidazole and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Midostaurin: (Major) The concomitant use of midostaurin and halogenated anesthetics may lead to additive QT interval prolongation. If these drugs are used together, consider electrocardiogram monitoring. In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin.
Mifepristone: (Major) Concomitant use of mifepristone and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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: (Major) Concomitant use of halogenated and mirtazapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mivacurium: (Moderate) Concomitant use of mivacurium and sevoflurane may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration. During maintenance of sevoflurane anesthesia, the mivacurium dose is likely to be reduced compared to that during nitrous oxide/opioid anesthesia. For endotracheal intubation, do not reduce the dose of mivacurium.
Mobocertinib: (Major) Concomitant use of mobocertinib and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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.
Moxifloxacin: (Major) According to the manufacturer, moxifloxacin should be avoided in patients taking drugs that can result in prolongation of the QT interval. Halogenated anesthetics can prolong the QT interval. Prolongation of the QT interval has been reported with administration of moxifloxacin. Post-marketing surveillance has identified very rare cases of ventricular arrhythmias including torsade de pointes (TdP), usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded.
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.
Naproxen; Pseudoephedrine: (Major) Avoid administration of pseudoephedrine products to patients who have recently undergone, or will soon undergo, a procedure or treatment that requires general anesthesia. Specifically, halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including pseudoephedrine.
Neostigmine: (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.
Neostigmine; Glycopyrrolate: (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.
Nesiritide, BNP: (Major) The potential for hypotension may be increased when coadministering nesiritide with other hypotensive drugs, including general anesthetics.
Nilotinib: (Major) Avoid the concomitant use of nilotinib and halogenated anesthetics; significant prolongation of the QT interval may occur. Sudden death and QT prolongation have been reported in patients who received nilotinib therapy. Additionally, fatal cases of torsade de pointes have been reported with halogenated anesthetic use.
Norepinephrine: (Moderate) Monitor cardiac rhythm in patients receiving norepinephrine with halogenated anesthetics. Concomitant use of may lead to ventricular tachycardia or ventricular fibrillation.
Ofloxacin: (Major) Concomitant use of ofloxacin and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Olanzapine: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with olanzapine. Halogenated anesthetics can prolong the QT interval. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. Therefore, caution is advised when administering olanzapine with drugs having an established causal association with QT prolongation and torsade de pointes (TdP).
Olanzapine; Fluoxetine: (Major) Concomitant use of halogenated anesthetics and fluoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. (Major) Halogenated anesthetics should be used cautiously and with close monitoring with olanzapine. Halogenated anesthetics can prolong the QT interval. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. Therefore, caution is advised when administering olanzapine with drugs having an established causal association with QT prolongation and torsade de pointes (TdP).
Olanzapine; Samidorphan: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with olanzapine. Halogenated anesthetics can prolong the QT interval. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. Therefore, caution is advised when administering olanzapine with drugs having an established causal association with QT prolongation and torsade de pointes (TdP).
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.
Ondansetron: (Major) Concomitant use of ondansetron and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Do not exceed 16 mg of IV ondansetron in a single dose; the degree of QT prolongation associated with ondansetron significantly increases above this dose.
Orphenadrine: (Moderate) General anesthetics potentiate the effects of other CNS depressants, including skeletal muscle relaxants.
Osilodrostat: (Major) Monitor ECGs in patients receiving osilodrostat with halogenated anesthetics. Osilodrostat is associated with dose-dependent QT prolongation. Halogenated anesthetics can prolong the QT interval.
Osimertinib: (Major) Avoid coadministration of halogenated anesthetics with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Halogenated anesthetics can also prolong the QT interval.
Oxaliplatin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of halogenated anesthetics with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Halogenated anesthetics can prolong the QT interval; QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
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.
Ozanimod: (Major) In general, do not initiate ozanimod in patients taking halogenated anesthetics due to the r isk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Halogenated anesthetics can prolong the QT interval.
Pacritinib: (Major) Concomitant use of pacritinib and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Paliperidone: (Major) Halogenated anesthetics can prolong the QT interval. Paliperidone has been associated with QT prolongation; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose. According to the manufacturer, since paliperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect, such as halogenated anesthetics. However, if coadministration is necessary and the patient has known risk factors for cardiac disease or arrhythmias, close monitoring is essential.
Pancuronium: (Moderate) Reduce the initial pancuronium dose if pancuronium is first administered after establishment of steady-state sevoflurane anesthesia. Consider the relatively long duration of action of pancuronium when the drug is selected for intubation in these circumstances. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration. The neuromuscular blocking action of pancuronium is potentiated by sevoflurane anesthesia. Recommended initial doses of pancuronium may be used to facilitate tracheal intubation before administration of sevoflurane.
Panobinostat: (Major) QT prolongation has been reported with panobinostat therapy in patients with multiple myeloma in a clinical trial; use of panobinostat with other agents that prolong the QT interval is not recommended. Obtain an electrocardiogram at baseline and periodically during treatment. Hold panobinostat if the QTcF increases to >= 480 milliseconds during therapy; permanently discontinue if QT prolongation does not resolve. Drugs with a possible risk for QT prolongation and torsade de pointes that should be used cautiously and with close monitoring with panobinostat include halogenated anesthetics.
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.
Pasireotide: (Major) Cautious use of pasireotide and drugs that prolong the QT interval, such as halogenated anesthetics, is needed, as coadministration may have additive effects on the prolongation of the QT interval.
Pazopanib: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and TdP that should be avoided with pazopanib include halogenated anesthetics.
Pentamidine: (Major) Pentamidine has been associated with serious cardiac arrhythmias including QT prolongation, and is considered to have an established risk of torsades de pointes. The drug should be used cautiously, if at all, in patients receiving agents which may cause QT prolongation or torsade de pointes including halogenated anesthetics such as sevoflurane.
Pentobarbital: (Moderate) Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
Perphenazine: (Minor) Halogenated anesthetics should be used cautiously and with close monitoring with perphenazine. Halogenated anesthetics can prolong the QT interval. Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. In addition, Phenothiazines can potentiate the CNS-depressant action of halogenated anesthetics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects.
Perphenazine; Amitriptyline: (Minor) Halogenated anesthetics should be used cautiously and with close monitoring with perphenazine. Halogenated anesthetics can prolong the QT interval. Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. In addition, Phenothiazines can potentiate the CNS-depressant action of halogenated anesthetics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects.
Phendimetrazine: (Major) Halogenated anesthetics, such as sevoflurane, sensitize the myocardium to the effects of sympathomimetics, such as phendimetrazine. Chronic use of sympathomimetics prior to halogenated anesthetics may result in cardiac arrhythmias. Phendimetrazine should be discontinued several days prior to surgery using halogenated anesthetics.
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.
Phentermine: (Major) Halogenated anesthetics may sensitize the myocardium to the effects of the sympathomimetics. Because of this, and its effects on blood pressure, phentermine should be discontinued several days prior to surgery.
Phentermine; Topiramate: (Major) Halogenated anesthetics may sensitize the myocardium to the effects of the sympathomimetics. Because of this, and its effects on blood pressure, phentermine should be discontinued several days prior to surgery.
Phenylephrine: (Major) Halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including phenylephrine, which can increase the risk of developing cardiac arrhythmias and hypotension.
Phenytoin: (Moderate) Caution is advised with the concomitant use of sevoflurane and phenytoin as concurrent use may increase the risk of hepatotoxicity.
Physostigmine: (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.
Pimavanserin: (Major) Pimavanserin may cause QT prolongation and should generally be avoided in patients receiving other medications known to prolong the QT interval, such as halogenated anesthetics. Coadministration may increase the risk for QT prolongation. Patients should discuss their medication regimen with their surgeon or anesthesiologist prior to any surgical or other procedures with these anesthetics.
Pimozide: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of sevoflurane with pimozide is contraindicated.
Pitolisant: (Major) Avoid coadministration of pitolisant with halogenated anesthetics as concurrent use may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. Halogenated anesthetics can also prolong the QT interval.
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.
Ponesimod: (Major) In general, do not initiate ponesimod in patients taking halogenated anesthetics due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Halogenated anesthetics can prolong the QT interval.
Posaconazole: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with posaconazole. Halogenated anesthetics can prolong the QT interval. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes.
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) Local anesthetics may result in QT prolongation and should be used with caution with other agents that can prolong the QT interval including halogenated anesthetics (i.e., desflurane, enflurane, halothane, isoflurane, and sevoflurane). Also, If epinephrine is added to prilocaine, do not use the mixture in a patient during or following treatment with general anesthetics. Concurrent use has been associated with the development of cardiac arrhythmias, and should be avoided, if possible. (Moderate) Monitor patients who are concomitantly receiving epinephrine and sevoflurane for the development of arrhythmias. Halogenated anesthetics, such as sevoflurane, sensitize the myocardium and may potentiate the arrhythmogenic effects of epinephrine. If occur, such arrhythmias may respond to beta-blocker administration. A study investigating the epinephrine induced arrhythmogenic effect of sevoflurane in adult patients undergoing transsphenoidal hypophysectomy demonstrated that the threshold dose of epinephrine (i.e., the dose at which the first sign of arrhythmia was observed) producing multiple ventricular arrhythmias was 5 mcg/kg.
Primaquine: (Major) Due to the potential for QT interval prolongation with primaquine, caution is advised with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with primaquine include halogenated anesthetics.
Primidone: (Moderate) Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
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: (Minor) Halogenated anesthetics should be used cautiously and with close monitoring with prochlorperazine. Halogenated anesthetics can prolong the QT interval. Phenothiazines have been reported to prolong the QT interval. Concurrent use of drugs that are associated with a possible risk for QT prolongation and torsade de pointes (TdP) with prochlorperazine should be approached with caution. If coadministration is considered necessary, and the patient has known risk factors for cardiac disease or arrhythmia, then close monitoring is essential. In addition, additive CNS effects (e.g., oversedation, respiratory depression, and hypotension) may occur if prochlorperazine is administered concomitantly with halogenated anesthetics.
Promethazine: (Moderate) Halogenated anesthetics carry a possible risk for QT prolongation and torsade de pointes (TdP). Promethazine carries a possible risk of QT prolongation and should be used cautiously with these anesthetics, with proper blood pressure and heart rate monitoring.
Promethazine; Dextromethorphan: (Moderate) Halogenated anesthetics carry a possible risk for QT prolongation and torsade de pointes (TdP). Promethazine carries a possible risk of QT prolongation and should be used cautiously with these anesthetics, with proper blood pressure and heart rate monitoring.
Promethazine; Phenylephrine: (Major) Halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including phenylephrine, which can increase the risk of developing cardiac arrhythmias and hypotension. (Moderate) Halogenated anesthetics carry a possible risk for QT prolongation and torsade de pointes (TdP). Promethazine carries a possible risk of QT prolongation and should be used cautiously with these anesthetics, with proper blood pressure and heart rate monitoring.
Propafenone: (Major) Concomitant use of propafenone and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Pseudoephedrine: (Major) Avoid administration of pseudoephedrine products to patients who have recently undergone, or will soon undergo, a procedure or treatment that requires general anesthesia. Specifically, halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including pseudoephedrine.
Pseudoephedrine; Triprolidine: (Major) Avoid administration of pseudoephedrine products to patients who have recently undergone, or will soon undergo, a procedure or treatment that requires general anesthesia. Specifically, halogenated anesthetics may sensitize the myocardium to the effects of sympathomimetics, including pseudoephedrine. (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Pyridostigmine: (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.
Pyrilamine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Quetiapine: (Major) Concomitant use of quetiapine and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quinine: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including halogenated anesthetics.
Quizartinib: (Major) Concomitant use of quizartinib and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ranolazine: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with ranolazine. Halogenated anesthetics can prolong the QT interval. Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. The mean increase in QTc is about 6 milliseconds, measured at the tmax of the maximum dosage (1000 mg PO twice daily). However, in 5% of the population studied, increases in the QTc of at least 15 milliseconds have been reported. Although there are no studies examining the effects of ranolazine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
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.
Relugolix: (Major) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents such as halogenated anesthetics. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Halogenated anesthetics can also prolong the QT interval.
Relugolix; Estradiol; Norethindrone acetate: (Major) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents such as halogenated anesthetics. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Halogenated anesthetics can also prolong the QT interval.
Remifentanil: (Moderate) Concurrent use of sevoflurane with opiate agonists such as remifentanil can reduce the minimal alveolar concentration (MAC) and increase the CNS depression, hypotension, and respiratory depression associated with sevoflurane administration. However, concurrent use of sevoflurane is compatible with opioids is common in surgical practice.
Ribociclib: (Major) Avoid coadministration of ribociclib with halogenated anesthetics due to an increased risk for QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Halogenated anesthetics can also prolong the QT interval. Concomitant use may increase the risk for QT prolongation.
Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with halogenated anesthetics due to an increased risk for QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Halogenated anesthetics can also prolong the QT interval. Concomitant use may increase the risk for QT prolongation.
Rifampin: (Moderate) Caution is advised with the concomitant use of sevoflurane and rifampin as concurrent use may increase the risk of hepatotoxicity.
Rilpivirine: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with rilpivirine. Halogenated anesthetics can prolong the QT interval. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval.
Risperidone: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with risperidone. Halogenated anesthetics can prolong the QT interval. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, taking into account the patient's underlying disease state(s) and additional potential risk factors.
Rivastigmine: (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.
Rocuronium: (Moderate) Concomitant use of rocuronium and sevoflurane may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration. During maintenance of sevoflurane anesthesia, the rocuronium dose is likely to be reduced compared to that during nitrous oxide/opioid anesthesia. For endotracheal intubation, do not reduce the dose of rocuronium.
Romidepsin: (Major) Romidepsin has been reported to prolong the QT interval. Halogenated anesthetics can prolong the QT interval. If romidepsin must be coadministered with a halogenated anesthetic, appropriate cardiovascular monitoring precautions should be considered, such as the monitoring of electrolytes and ECGs at baseline and periodically during treatment.
Saquinavir: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with saquinavir. Halogenated anesthetics can prolong the QT interval. Saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as torsades de pointes (TdP). Avoid administering saquinavir boosted with ritonavir concurrently with other drugs that may prolong the QT interval. If no acceptable alternative therapy is available, perform a baseline ECG prior to initiation of concomitant therapy and carefully follow monitoring recommendations.
Secobarbital: (Moderate) Additive CNS depression may occur if general anesthetics are used concomitantly with barbiturates.
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.
Selpercatinib: (Major) Monitor ECGs more frequently for QT prolongation if coadministration of selpercatinib with halogenated anesthetics is necessary due to the risk of additive QT prolongation. Concentration-dependent QT prolongation has been observed with selpercatinib therapy. Halogenated anesthetics can prolong the QT interval.
Sertraline: (Major) Concomitant use of sertraline and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with sertraline is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 2 times the maximum recommended dose.
Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving halogenated anesthetics due to the potential for QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Halogenated anesthetics can prolong the QT interval.
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.
Sodium Stibogluconate: (Major) Concomitant use of sodium stibogluconate and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Solifenacin: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with solifenacin. Halogenated anesthetics can prolong the QT interval. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation.
Sorafenib: (Major) Avoid coadministration of sorafenib with halogenated anesthetics due to the risk of additive QT prolongation. If concomitant use is unavoidable, monitor electrocardiograms and correct electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Sorafenib is associated with QTc prolongation. Halogenated anesthetics can also prolong the QT interval.
Sotalol: (Major) General anesthetics can potentiate the antihypertensive effects of beta-blockers and can produce prolonged hypotension. Severe, protracted hypotension and difficulty in restarting the heart have been reported after surgery on patients receiving beta-blockers. In addition, sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Drugs with a possible risk for QT prolongation and TdP, such as halogenated anesthetics, should be used cautiously with sotalol.
St. John's Wort, Hypericum perforatum: (Major) St. John's wort, Hypericum perforatum, may intensify or prolong the effects of sevoflurane; 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.
Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and general anesthetics. CNS depressants can potentiate the effects of stiripentol.
Streptomycin: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving streptomycin.
Succinylcholine: (Moderate) Additional monitoring or a dosage reduction may be required for some patients during concomitant use of succinylcholine and sevoflurane. Concomitant use may prolong neuromuscular blockade and increase the risk for hyperkalemia and malignant hyperthermia.
Sufentanil: (Moderate) The magnitude and duration of central nervous system and cardiovascular effects may be enhanced when sufentanil is administered to patients receiving sevoflurane. Prolonged recovery time may occur. When used together, doses of sufentanil and/or sevoflurane should be reduced and titrated carefully.
Sunitinib: (Major) Monitor patients for QT prolongation if coadministration of halogenated anesthetics with sunitinib is necessary. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Halogenated anesthetics can also prolong the QT interval.
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.
Tacrolimus: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with tacrolimus. Halogenated anesthetics and tacrolimus can prolong the QT interval.
Tamoxifen: (Major) Concomitant use of tamoxifen and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
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.
Telavancin: (Major) Telavancin has been associated with QT prolongation. According to the manufacturer, telavancin should be used with caution when prescribing other agents also known to prolong the QT interval (e.g., halogenated anesthetics).
Terazosin: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Tetrabenazine: (Major) Tetrabenazine causes a small increase in the corrected QT interval. The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc including halogenated anesthetics.
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. A similar interaction may occur with other general anesthetics.
Thiazide diuretics: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Thioridazine: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension, such as halogenated anesthetics.
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.
Tolterodine: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with tolterodine. Halogenated anesthetics can prolong the QT interval. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. This should be taken into consideration when prescribing tolterodine to patients taking other drugs that are associated with QT prolongation.
Toremifene: (Major) Avoid coadministration of halogenated anesthetics with toremifene if possible due to the risk of additive QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia or hypomagnesemia prior to administration of toremifene. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. Halogenated anesthetics can also prolong the QT interval.
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.
Trazodone: (Major) Concomitant use of trazodone and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Treprostinil: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Triclabendazole: (Major) Concomitant use of triclabendazole and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Tricyclic antidepressants: (Minor) Tricyclic antidepressants (TCAs) should be used cautiously and with close monitoring with halogenated anesthetics. Halogenated anesthetics can prolong the QT interval. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). In addition, general anesthetics may produce additive CNS depression when used in patients taking tricyclic antidepressants.
Trifluoperazine: (Minor) Halogenated anesthetics should be used cautiously and with close monitoring with trifluoperazine. Halogenated anesthetics can prolong the QT interval. Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation. In addition, phenothiazines can potentiate the CNS-depressant action of halogenated anesthetics.
Triprolidine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Triptorelin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving halogenated anesthetics. Androgen deprivation therapy may prolong the QT/QTc interval. Halogenated anesthetics can also prolong the QT interval.
Vancomycin: (Moderate) The concurrent administration of vancomycin and anesthetics has been associated with erythema, histamine-like flushing, and anaphylactoid reactions.
Vandetanib: (Major) Avoid coadministration of vandetanib with halogenated anesthetics due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Halogenated anesthetics can also prolong the QT interval.
Vardenafil: (Major) Concomitant use of vardenafil and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Vasodilators: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Vecuronium: (Moderate) Reduce the initial vecuronium dose by approximately 15% (i.e., to 0.06 to 0.085 mg/kg) if vecuronium is first administered more than 5 minutes after the start of sevoflurane or when steady-state has been achieved. It may be necessary to reduce the vecuronium infusion rate by 25% to 60% at 45 to 60 minutes after the intubating dose in the presence of steady-state concentrations of sevoflurane. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration. The neuromuscular blocking action of vecuronium is potentiated by sevoflurane anesthesia.
Vemurafenib: (Major) Vemurafenib has been associated with QT prolongation. If vemurafenib and another drug that is associated with a possible risk for QT prolongation and torsade de pointes (TdP) must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with vemurafenib include halogenated anesthetics.
Venlafaxine: (Major) Concomitant use of venlafaxine and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Voclosporin: (Major) Use caution if halogenated anesthetics are coadministered with voclosporin due to the risk of additive QT prolongation. Halogenated anesthetics can prolong the QT interval. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with clarithromycin. Halogenated anesthetics can prolong the QT interval and clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP).
Voriconazole: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with voriconazole. Halogenated anesthetics can prolong the QT interval. Voriconazole has been associated with QT prolongation and rare cases of torsades de pointes.
Vorinostat: (Major) Vorinostat and halogenated anesthetics are associated with a risk of QT prolongation and should be used cautiously in combination.
Warfarin: (Minor) Sevoflurane may increase the effects of warfarin. Another halogenated anesthetic, halothane, has been associated with an increase in activity of warfarin. The trifluoroacetic acid metabolite of halothane appears to displace warfarin from plasma proteins, which may increase the free-fraction of warfarin. The effects of sevoflurane on the displacement of drugs from serum and tissue proteins have not been investigated.
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.
Ziprasidone: (Major) Concomitant use of ziprasidone and sevoflurane should be avoided due to the potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. Halogenated anesthetics, such as sevoflurane, can prolong the QT interval.
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.

How Supplied

Sevoflurane/Ultane Respiratory (Inhalation) Liq: 100%

Maximum Dosage
Adults

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

Elderly

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

Adolescents

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

Children

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

Mechanism Of Action

Mechanism of Action: The exact mechanism of action of inhalational anesthetics is not known. There appears to be a correlation between anesthetic potency and lipid solubility (Meyer-Overton theory), suggesting that inhalation anesthetics likely affect the lipid matrix of nerve cell membranes in the brain. Furthermore, NMR and electron spin resonance studies indicate that anesthetics cause a local disordering of the lipid membrane matrix, possibly decreasing the number of molecules that alternate simultaneously between the gel and crystalline states, and thereby altering membrane function.

Pharmacokinetics

Sevoflurane is administered by inhalation. In 40-year old adults, the MAC value (minimal alveolar concentration that prevents movements in 50% of patients subjected to a painful stimulus) of sevoflurane is 2.1% when mixed in oxygen, which is roughly equivalent to enflurane. The MAC of sevoflurane decreases with age. Due to the low solubility of sevoflurane in blood (blood/gas coefficient at 37 degrees C is 0.63—0.69), a minimal amount of sevoflurane is required to be dissolved in the blood before alveolar partial pressure is in equilibrium with arterial partial pressure. Therefore, the alveolar (end-tidal) concentration rapidly increases to the inspired concentration during induction. The time for the concentration to reach MAC for sevoflurane is about 1 minute in healthy men. Metabolism and tissue elimination of sevoflurane is similar to isoflurane and enflurane, but distinct from that of methoxyflurane. The rapid and extensive pulmonary elimination of sevoflurane minimizes the amount of anesthetic available for metabolism. In vivo studies suggest that only about 5% of the sevoflurane dose is metabolized. Sevoflurane is metabolized by the hepatic cytochrome P4502E1 isoenzyme to hexafluoroisopropanol (HFIP) with the release of inorganic fluoride and carbon dioxide. HFIP is rapidly conjugated with glucuronic acid and excreted in the urine. Plasma concentration of fluoride ion is influenced by the duration of anesthesia, the concentration of sevoflurane administered, and the composition of the anesthetic gas mixture. In studies where pure sevoflurane was administered for 1—6 hours, peak fluoride concentrations ranged between 12—90 microM. Peak concentrations of fluoride ion occur within 2 hours of the end of anesthesia and are < 25 microM (475 ng/ml) for the majority of patients after 10 hours. Approximately 3.5% of the administered sevoflurane dose appears in the urine as fluoride and 50% of fluoride clearance is due to fluoride being taken up into bone. The half-life of fluoride is about 15—23 hours.

Inhalation Route

Following inhalation, sevoflurane is readily absorbed via the pulmonary capillary system.

Pregnancy And Lactation
Pregnancy

No adequate and well-controlled studies of sevoflurane have been conducted in pregnant women. Reduced fetal weights were noted in animal reproduction studies with sevoflurane. 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. Chronic accidental exposure to inhalational anesthetics, as can occur in operating room personnel, may increase the risk for miscarriage. Sevoflurane has been used as part of general anesthesia for elective cesarean section with no untoward effects in mother or neonate. However, the safety of sevoflurane in labor and obstetric delivery has not been established. Sevoflurane can cause uterine smooth muscle relaxation and may contribute to uterine atony.