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Sevoflurane: Drug information

Sevoflurane: Drug information
(For additional information see "Sevoflurane: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Ultane
Pharmacologic Category
  • General Anesthetic, Inhalation
Dosing: Adult
Anesthesia

Anesthesia: Inhalation: Surgical levels of anesthesia are generally achieved with concentrations from 0.5% to 3% with or without the concomitant use of nitrous oxide; the concentration at which amnesia and loss of awareness occur is 0.6% (Ref).

MAC values for surgical levels of anesthesia:

25 years:

Sevoflurane in oxygen: 2.6%

Sevoflurane in 65% N20/35% oxygen: 1.4%

40 years:

Sevoflurane in oxygen: 2.1%

Sevoflurane in 65% N20/35% oxygen: 1.1%

60 years:

Sevoflurane in oxygen: 1.7%

Sevoflurane in 65% N20/35% oxygen: 0.9%

80 years:

Sevoflurane in oxygen: 1.4%

Sevoflurane in 65% N20/35% oxygen: 0.7%

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in manufacturer's labeling; use with caution in patients with creatinine >1.5 mg/dL (safety not established).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in manufacturer's labeling; use with caution (safety with severe hepatic impairment has not been studied).

Dosing: Older Adult

Refer to adult dosing. MAC is reduced in the elderly (50% reduction by age 80).

Dosing: Pediatric
Anesthesia

Anesthesia: Inhalation: Surgical levels of anesthesia are generally achieved with concentrations from 0.5% to 3% with or without the concomitant use of nitrous oxide; the concentration at which amnesia and loss of awareness occur is 0.6% (Ref).

MAC values for surgical levels of anesthesia:

0 to 1 month old full-term neonates: Sevoflurane in oxygen: 3.3%

1 to <6 months: Sevoflurane in oxygen: 3%

6 months to <1 year:

Sevoflurane in oxygen: 2.8%

Sevoflurane in 65% N20/35% oxygen: 2%

1 to <3 years:

Sevoflurane in oxygen: 2.8%

Sevoflurane in 60% N20/40% oxygen: 2%

3 to 12 years: Sevoflurane in oxygen: 2.5%

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in manufacturer's labeling; use with caution; has not been studied in adult patients with elevated SCr.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in manufacturer's labeling; use with caution (safety with severe hepatic impairment has not been studied).

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adult and pediatric patients.

>10%:

Cardiovascular: Hypotension (4% to 11%)

Gastrointestinal: Nausea (25%), vomiting (18%)

Nervous system: Agitation (7% to 15%)

Respiratory: Increased cough (5% to 11%)

1% to 10%:

Cardiovascular: Bradycardia (5%), hypertension (2%), tachycardia (2% to 6%)

Gastrointestinal: Sialorrhea (2% to 4%)

Nervous system: Dizziness (4%), drowsiness (9%), headache (1%), hypothermia (1%), myoclonus (1%), shivering (6%)

Neuromuscular & skeletal: Laryngospasm (2% to 8%)

Respiratory: Airway obstruction (8%), apnea (2%), breath-holding (2% to 5%)

Miscellaneous: Fever (1%)

<1%:

Cardiovascular: Atrial arrhythmia, atrial fibrillation, bigeminy, cardiac arrhythmia, complete atrioventricular block, depression of ST segment on ECG, inversion T wave on ECG, second degree atrioventricular block, supraventricular extrasystole, syncope, ventricular premature contractions

Dermatologic: Pruritus, skin rash

Endocrine & metabolic: Acidosis, albuminuria, glycosuria, hyperglycemia, hypophosphatemia, increased lactate dehydrogenase

Gastrointestinal: Dental fluorosis, dysgeusia, hiccups, xerostomia

Genitourinary: Oliguria, urinary retention, urination disorder, urine abnormality

Hematologic & oncologic: Hemorrhage, leukocytosis, thrombocytopenia

Hepatic: Hyperbilirubinemia, increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferase

Nervous system: Confusion, hypertonia, insomnia, malignant hyperthermia, nervousness, pain

Neuromuscular & skeletal: Asthenia

Ophthalmic: Amblyopia, conjunctivitis

Renal: Increased blood urea nitrogen, increased serum creatinine

Respiratory: Bronchospasm, dyspnea, hyperventilation, hypoventilation, hypoxia, increased bronchial secretions, pharyngitis, stridor, wheezing

Miscellaneous: Crying

Postmarketing:

Cardiovascular: Chest discomfort, prolonged QT interval on ECG, torsades de pointes

Hepatic: Hepatic failure, hepatic necrosis, hepatitis, hepatotoxicity (idiosyncratic; Chalasani 2014), jaundice

Hypersensitivity: Anaphylaxis, hypersensitivity reaction

Nervous system: Delirium, seizure

Contraindications

Hypersensitivity to sevoflurane, other halogenated inhalational anesthetics, or any component of the formulation; known or suspected genetic susceptibility to malignant hyperthermia.

Canadian labeling: Additional contraindications (not in US labeling): Occurrence of liver dysfunction, jaundice or unexplained fever, leukocytosis, or eosinophilia after previous halogenated anesthetic administration; when general anesthesia is contraindicated.

Warnings/Precautions

Concerns related to adverse effects:

• Agitation/delirium: Monitor for emergence agitation or delirium (Stachnik 2006).

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving).

• Hepatic effects: Postoperative hepatitis (eg, jaundice associated with fever and/or eosinophilia) or hepatic dysfunction has been reported; prior exposure to halogenated hydrocarbon anesthetics may increase this risk.

• Hyperkalemia: Use of inhaled anesthetics has been associated with rare cases of perioperative hyperkalemia in pediatric patients; concomitant use of succinylcholine was associated with most of the reported cases, but not all. Patients with latent and overt neuromuscular disease (eg, Duchenne muscular dystrophy) are the most vulnerable. Other abnormalities may include elevation in CPK and myoglobinuria. Monitor closely for arrhythmias. Aggressively identify and treat hyperkalemia and resistant arrhythmias.

• Hypotension: Sevoflurane produces a dose-dependent reduction in blood pressure during maintenance of anesthesia and may occur more rapidly compared to other inhaled anesthetics.

• Increased intracranial pressure: May dilate the cerebral vasculature and may, in certain conditions, increase intracranial pressure (Stachnik 2006).

• Malignant hyperthermia: May trigger malignant hyperthermia; some reported cases have been fatal. Risk may be increased with concomitant administration of succinylcholine and volatile anesthetic agents and patients with genetic factors or family history of malignant hyperthermia, including ryanodine receptor or dihydropyridine receptor inherited variants. Signs of malignant hyperthermia may include arrhythmias, cyanosis, hemodynamic instability, hypercapnia, hyperthermia, hypovolemia, hypoxia, muscle rigidity, tachycardia, and tachypnea; coagulopathies, renal failure, and skin mottling may also occur. If malignant hyperthermia is suspected, discontinue triggering agents and institute appropriate therapy (eg, dantrolene) and other supportive measures.

• QT prolongation: Cases of QT prolongation in association with torsade de pointes (some fatal) have been reported with sevoflurane use; use caution when administering to patients at risk of QT prolongation (eg, concurrent use of drugs that can prolong the QT interval such as class Ia and III antiarrhythmic drugs, elderly patients, congenital QT prolongation) (Han 2010; Kang 2006; Nakao 2010).

• Respiratory depression: May cause dose-dependent respiratory depression and blunted ventilatory response to hypoxia and hypercapnia (Golembiewski 2004); response may be augmented by other medications with respiratory depressant effect (eg, opioids). Hypoxic pulmonary vasoconstriction is blunted, which may lead to increased pulmonary shunt (Miller 2010).

Disease-related concerns:

• Heart failure: In a scientific statement from the American Heart Association, sevoflurane has been determined to be an agent that may exacerbate underlying myocardial dysfunction (magnitude: major) (AHA [Page 2016]).

• Hepatic impairment: Use with caution in patients with hepatic impairment; safety with severe impairment has not been established.

• Renal impairment: Use with caution in patients with renal impairment (ie, creatinine >1.5 mg/dL); safety with severe impairment has not been established.

• Seizure disorder: Use with caution in patients at risk for seizures; seizures have been reported in children and young adults.

Special populations:

• Pediatric neurotoxicity: In pediatric and neonatal patients <3 years and patients in third trimester of pregnancy (ie, times of rapid brain growth and synaptogenesis), the repeated or lengthy exposure to sedatives or anesthetics during surgery/procedures may have detrimental effects on child or fetal brain development and may contribute to various cognitive and behavioral problems. Epidemiological studies in humans have reported various cognitive and behavioral problems, including neurodevelopmental delay (and related diagnoses), learning disabilities, and ADHD. Human clinical data suggest that single, relatively short exposures are not likely to have similar negative effects. No specific anesthetic/sedative has been found to be safer. For elective procedures, risk vs benefits should be evaluated and discussed with parents/caregivers/patients; critical surgeries should not be delayed (FDA 2016).

Special handling:

• Occupational caution: There is no specific work exposure limit established for sevoflurane. However, the National Institute for Occupational Safety and Health (NIOSH) has recommended an 8 hour time-weighted average limit of 2 ppm for halogenated anesthetic agents in general (0.5 ppm when coupled with exposure to N2O).

Other warnings/precautions:

• Desiccated absorbents: Reaction of sevoflurane with CO2 absorbents that become desiccated within circle breathing equipment can lead to formation of formaldehyde (causing respiratory irritation) and carbon monoxide; maintain fresh absorbent as per manufacturer guidelines regardless of state of colorimetric indicator. An exothermic reaction occurs when sevoflurane is exposed to CO2 absorbents; this reaction is increased when the CO2 absorbent becomes desiccated. Rare cases of extreme heat, smoke, and/or fire within breathing circuit have been reported. This reaction also leads to formation of a fluorinated byproduct, compound A, which has been reported to cause mild and reversible renal injury in animal studies (Gentz 2001). The theoretical risk of compound A-induced nephrotoxicity in humans may be dose- and exposure time-dependent; minimize exposure risk by not exceeding 2 MAC hours and using fresh flow rates of 1 to <2 L/minute (low fresh gas flow rates maximize rebreathing of the anesthetic). Steps to help reduce the risk of these events (eg, shutting off the anesthesia machine at the end of clinical use or after any case when a subsequent extended period of nonuse is expected, routine replacement of the CO2 absorbents) should be incorporated into routine practice (Miller 2010).

Warnings: Additional Pediatric Considerations

Pediatric patients with trisomy 21 (Down syndrome) have been shown to be at an increased risk of developing bradycardia during anesthetic induction with sevoflurane. The mechanism for bradycardia is unknown. Some patients have failed to respond to traditional treatment options (eg, atropine). Dose reduction of sevoflurane and adequate oxygenation and ventilation were effective in most cases to reestablish baseline heart rates and hemodynamic stability (Bai 2010; Health Canada Safety Review 2018; Kraemer 2010; Roodman 2003; Walia 2016).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Inhalation:

Ultane: (250 mL)

Generic: (100 mL [DSC], 250 mL)

Generic Equivalent Available: US

Yes

Administration: Adult

Via sevoflurane-specific calibrated vaporizers; use cautiously in low-flow or closed-circuit systems since sevoflurane is unstable and potentially toxic breakdown products have been liberated.

Administration: Pediatric

Inhalation: Administer via sevoflurane-specific calibrated vaporizers; use cautiously in low-flow or closed-circuit systems since sevoflurane is unstable and potentially toxic breakdown products have been liberated.

Use: Labeled Indications

Anesthesia: Induction and maintenance of general anesthesia in adults and pediatric patients for inpatient and outpatient surgery

Medication Safety Issues
Sound-alike/look-alike issues:

Ultane may be confused with Ultram

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Metabolism/Transport Effects

Substrate of CYP2A6 (minor), CYP2B6 (minor), CYP2E1 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification

Amisulpride (Oral): May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk C: Monitor therapy

Amisulpride (Oral): May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy

Arginine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Bambuterol: May enhance the arrhythmogenic effect of Inhalational Anesthetics. Management: Some labels recommend specifically avoiding halothane; others recommend separating administration by at least 6 hours; other bambuterol labels do not mention this possible interaction. Monitor for increased sensitivity to arrhythmias if coadministered. Risk D: Consider therapy modification

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification

Calcium Channel Blockers: Inhalational Anesthetics may enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy

Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy

Dabrafenib: QT-Prolonging Inhalational Anesthetics (Moderate Risk) may enhance the QTc-prolonging effect of Dabrafenib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification

Dexmethylphenidate-Methylphenidate: May enhance the hypertensive effect of Inhalational Anesthetics. Risk X: Avoid combination

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Domperidone: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Domperidone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

DOPamine: Inhalational Anesthetics may enhance the arrhythmogenic effect of DOPamine. Risk C: Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Risk C: Monitor therapy

DroPERidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification

DroPERidol: May enhance the CNS depressant effect of QT-Prolonging Inhalational Anesthetics (Moderate Risk). DroPERidol may enhance the QTc-prolonging effect of QT-Prolonging Inhalational Anesthetics (Moderate Risk). Management: Consider dose reductions and monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy

Ephedra: May enhance the arrhythmogenic effect of Inhalational Anesthetics. Risk X: Avoid combination

EPHEDrine (Nasal): May enhance the arrhythmogenic effect of Inhalational Anesthetics. Risk X: Avoid combination

EPHEDrine (Systemic): May enhance the arrhythmogenic effect of Inhalational Anesthetics. Risk X: Avoid combination

EPINEPHrine (Nasal): Inhalational Anesthetics may enhance the arrhythmogenic effect of EPINEPHrine (Nasal). Risk C: Monitor therapy

EPINEPHrine (Oral Inhalation): Inhalational Anesthetics may enhance the arrhythmogenic effect of EPINEPHrine (Oral Inhalation). Risk C: Monitor therapy

EPINEPHrine (Systemic): Inhalational Anesthetics may enhance the arrhythmogenic effect of EPINEPHrine (Systemic). Management: Administer epinephrine with added caution in patients receiving, or who have recently received, inhalational anesthetics. Use lower than normal doses of epinephrine and monitor for the development of cardiac arrhythmias. Risk D: Consider therapy modification

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Fenoterol: Inhalational Anesthetics may enhance the arrhythmogenic effect of Fenoterol. Risk C: Monitor therapy

Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification

Fluorouracil Products: QT-Prolonging Inhalational Anesthetics (Moderate Risk) may enhance the QTc-prolonging effect of Fluorouracil Products. Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Haloperidol: May enhance the QTc-prolonging effect of QT-Prolonging Inhalational Anesthetics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Isoproterenol: Inhalational Anesthetics may enhance the arrhythmogenic effect of Isoproterenol. Risk X: Avoid combination

Ixabepilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification

Levodopa-Foslevodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Foslevodopa. Risk C: Monitor therapy

Levoketoconazole: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Levoketoconazole. Risk X: Avoid combination

Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Metaraminol: Inhalational Anesthetics may enhance the arrhythmogenic effect of Metaraminol. Risk X: Avoid combination

Methadone: QT-Prolonging Inhalational Anesthetics (Moderate Risk) may enhance the CNS depressant effect of Methadone. Methadone may enhance the QTc-prolonging effect of QT-Prolonging Inhalational Anesthetics (Moderate Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation, ventricular arrhythmias, sedation, and respiratory depression. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification

Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Monoamine Oxidase Inhibitors: May enhance the adverse/toxic effect of Sevoflurane. Specifically, the risk of hemodynamic instability may be increased. Risk C: Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Neuromuscular-Blocking Agents (Nondepolarizing): Inhalational Anesthetics may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Management: When initiating a non-depolarizing neuromuscular blocking agent (NMBA) in a patient receiving an inhalational anesthetic, initial NMBA doses should be reduced 15% to 25% and doses of continuous infusions should be reduced 30% to 60%. Risk D: Consider therapy modification

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy

Norepinephrine: Inhalational Anesthetics may enhance the arrhythmogenic effect of Norepinephrine. Risk C: Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification

Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Ondansetron: May enhance the QTc-prolonging effect of QT-Prolonging Inhalational Anesthetics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination

Pentamidine (Systemic): May enhance the QTc-prolonging effect of QT-Prolonging Inhalational Anesthetics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Phenylephrine (Ophthalmic): May enhance the adverse/toxic effect of Inhalational Anesthetics. Specifically, the cardiovascular depressant effects of inhalational anesthetics may be increased. Risk C: Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Pimozide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy

Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

QT-prolonging Agents (Highest Risk): QT-Prolonging Inhalational Anesthetics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-prolonging Antidepressants (Moderate Risk): QT-Prolonging Inhalational Anesthetics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Antipsychotics (Moderate Risk): QT-Prolonging Inhalational Anesthetics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Class IC Antiarrhythmics (Moderate Risk): QT-Prolonging Inhalational Anesthetics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Class IC Antiarrhythmics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-Prolonging Inhalational Anesthetics (Moderate Risk): May enhance the hypotensive effect of other QT-Prolonging Inhalational Anesthetics (Moderate Risk). QT-Prolonging Inhalational Anesthetics (Moderate Risk) may enhance the QTc-prolonging effect of other QT-Prolonging Inhalational Anesthetics (Moderate Risk). Management: Monitor for hypotension and QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Kinase Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QT-Prolonging Inhalational Anesthetics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Miscellaneous Agents (Moderate Risk): May enhance the QTc-prolonging effect of QT-Prolonging Inhalational Anesthetics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): QT-Prolonging Inhalational Anesthetics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Quinolone Antibiotics (Moderate Risk): QT-Prolonging Inhalational Anesthetics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Quinolone Antibiotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QT-Prolonging Inhalational Anesthetics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Ritodrine: May enhance the adverse/toxic effect of Inhalational Anesthetics. Risk C: Monitor therapy

Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy

Sertindole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination

Silodosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification

Zuranolone: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider therapy modification

Pregnancy Considerations

Sevoflurane crosses the placenta (Satoh 1995).

Based on animal data, repeated or prolonged use of general anesthetic and sedation medications that block N-methyl-D- aspartate (NMDA) receptors and/or potentiate gamma-aminobutyric acid (GABA) activity, may affect brain development. Evaluate benefits and potential risks of fetal exposure to sevoflurane when duration of surgery is expected to be >3 hours (Olutoye 2018).

Use of sevoflurane in obstetric anesthesia has been described (ACOG 209 2019; Choi 2012; Devroe 2015; Gambling 1995; Karaman 2006). Maternal exposure should be minimized due to dose dependent uterine relaxation and fetal depression (ACOG 209 2019; Devroe 2015). Adverse events have not been observed following use as part of general anesthesia for elective cesarean delivery.

The ACOG recommends that pregnant women should not be denied medically necessary surgery, regardless of trimester. If the procedure is elective, it should be delayed until after delivery (ACOG 775 2019).

Breastfeeding Considerations

It is not known if sevoflurane is present in breast milk.

Patients can express and discard milk for the first 24 hours after administration to minimize infant exposure via breast milk.

The Academy of Breastfeeding Medicine recommends postponing elective surgery until milk supply and breastfeeding are established. Milk should be expressed ahead of surgery when possible. In general, when the child is healthy and full term, breastfeeding may resume, or milk may be expressed once the mother is awake and in recovery. For children who are at risk for apnea, hypotension, or hypotonia, milk may be saved for later use when the child is at lower risk (ABM [Reece-Stremtan 2017]).

Monitoring Parameters

BP, temperature, heart rate and rhythm, respiration, oxygen saturation, end-tidal CO2 and end-tidal sevoflurane concentrations should be monitored prior to and throughout anesthesia; temperature of CO2 absorbent canister

Mechanism of Action

Inhaled anesthetics alter activity of neuronal ion channels particularly the fast synaptic neurotransmitter receptors (nicotinic acetylcholine, GABA, and glutamate receptors). Limited effects on sympathetic stimulation including cardiovascular system. Sevoflurane does not cause respiratory irritation or circulatory stimulation. May depress myocardial contractility, decrease blood pressure through a decrease in systemic vascular resistance and decrease sympathetic nervous activity.

Pharmacokinetics (Adult Data Unless Noted)

Sevoflurane has a low blood/gas partition coefficient and therefore is associated with a rapid onset of anesthesia and recovery

Onset of action: Time to induction: Within 2 to 3 minutes

Duration: Emergence time: Depends on blood concentration when sevoflurane is discontinued. The rate of change of anesthetic concentration in the lung is rapid with sevoflurane because of its low blood gas solubility (0.63). The 90% decrement time (time required for anesthetic concentration in vessel-rich tissues to decrease by 90%) for sevoflurane is short when the duration of anesthesia is <2 hours but increases dramatically as the duration of administration is lengthened (Bailey, 1997).

Metabolism: Hepatic (~5%) via CYP2E1

Excretion: Exhaled gases

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AR) Argentina: Eraldin | Sevocris | Sevocristalia | Sevoflurano baxter | Sevomax | Sevorane;
  • (AT) Austria: Sevofluran baxter | Sevorane;
  • (AU) Australia: Sevorane;
  • (BD) Bangladesh: Sevorane;
  • (BE) Belgium: Sevoflurane baxter | Sevorane;
  • (BG) Bulgaria: Sevorane;
  • (BR) Brazil: Anesevo | Sevocris | Sevoflurano | Sevoness | Voflur;
  • (CH) Switzerland: Sevoflurane baxter;
  • (CN) China: Kai te li | Qi fu mei | Qifumei | Yi jun ning;
  • (CO) Colombia: Bloktec | Sevoflurano | Sevorane;
  • (CZ) Czech Republic: Sevorane | Sojourn;
  • (DE) Germany: Sevorane;
  • (DK) Denmark: Sevorane;
  • (DO) Dominican Republic: Sevorane;
  • (EC) Ecuador: Seflur | Sevoflurano | Sevorane;
  • (EE) Estonia: Sevoflurane baxter | Sevoflurane piramal | Sevorane;
  • (EG) Egypt: Sevoflurane usp;
  • (ES) Spain: Sevoflurano | Sevoflurano baxter | Sevoflurano piramal | Sevorane;
  • (FI) Finland: Sevorane;
  • (FR) France: Sevoflurane baxter | Sevorane;
  • (GB) United Kingdom: Sevoflurane abbott | Sevorane;
  • (GR) Greece: Sevorane;
  • (HK) Hong Kong: Sevorane;
  • (HR) Croatia: Sevofluran baxter | Sevorane;
  • (HU) Hungary: Sevoflurane baxter | Sevoflurane piramal | Sevorane;
  • (ID) Indonesia: Sevodex | Sevorane | Sojourn;
  • (IE) Ireland: Sevoflurane baxter | Sevorane;
  • (IN) India: Sevorane | Sevotroy | Sevura | Sojourn;
  • (IT) Italy: Sevoflurane baxter | Sevoflurane piramal | Sevorane;
  • (JP) Japan: Sevofrane abbott | Sevofrane aventis | Sevofrane maruishi | Sevoness;
  • (KR) Korea, Republic of: Baxter sevoflurane | Sevofran | Sevofrane | Sevoprane | Sevorane | Sojourn;
  • (LT) Lithuania: Sevoflurane baxter | Sevoflurane piramal | Sevorane;
  • (LV) Latvia: Sevoflurane piramal | Sevoran | Sevorane;
  • (MX) Mexico: Fhadotil | Floves | Savannlab | Sevam | Sevoflurano | Sevorane | Sovener | Svofast | Zurenpharm;
  • (MY) Malaysia: Sevorane | Sojourn;
  • (NG) Nigeria: Ultane;
  • (NL) Netherlands: Sevoflurane baxter | Sevorane;
  • (NO) Norway: Servofluran Baxter | Sevorane;
  • (NZ) New Zealand: Sevorane;
  • (PE) Peru: Inharane | Sevogesic | Sevorane | Sojourn;
  • (PH) Philippines: Baxter sevoflurane | Sevo | Sevorane | Sojourn;
  • (PK) Pakistan: Sevorane | Sojourn;
  • (PL) Poland: Sevoflurane baxter | Sevorane | Sojourn;
  • (PR) Puerto Rico: Sojourn | Ultane;
  • (PT) Portugal: Sevoflurano | Sevoflurano ojourn | Sevorane;
  • (PY) Paraguay: Eraldin | Floves | Sevocris | Sevoflurano omicron | Sevoflurano prosalud | Sevoflurano quimfa | Sevoflurano usp interlabo | Sevorane;
  • (RO) Romania: Sevo anesteran;
  • (RU) Russian Federation: Sevofluran medisorb | Sevofluran vial | Sevoflurane vial | Sevorane | Sojurne;
  • (SA) Saudi Arabia: Sojourn;
  • (SE) Sweden: Sevofluran baxter | Sevorane;
  • (SG) Singapore: Sevorane | Sojourn;
  • (SI) Slovenia: Sevofluran baxter | Sevofluran piramal | Sevorane;
  • (SK) Slovakia: Sevofluran baxter | Sevorane;
  • (TH) Thailand: Sefether | Sevoflurane baxter | Sevorane | Sojourn;
  • (TN) Tunisia: Sevorane;
  • (TR) Turkey: Sevoflurane baxter | Sevorane | Sojourn;
  • (TW) Taiwan: Sevoflurane baxter | Sevofrane | Sojourn | Ultane;
  • (UA) Ukraine: Sevo anesteran | Sevorane;
  • (UG) Uganda: Sevotroy;
  • (UY) Uruguay: Sevocris | Sevorane | Sojourn;
  • (VE) Venezuela, Bolivarian Republic of: Sevorane | Sojourn;
  • (ZA) South Africa: Sojourn | Ultane;
  • (ZM) Zambia: Ultane;
  • (ZW) Zimbabwe: Ultane
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