Sevoflorane

Pharmacologic Category

General Anesthetic, Inhalation

Dosing: Adult

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% (Katoh 1998).

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%

Dosing: Geriatric

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

Dosing: Renal 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: Pediatric

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% (Katoh 1998).

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%

Dosing: Renal 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).

Use: Labeled Indications

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

Clinical Practice Guidelines

Drug-Induced Liver Injury:

American College of Gastroenterology (ACG), “2014 ACG Guideline for Idiosyncratic Drug-induced Liver Injury,” July 2014

Administration: Inhalation

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.

Storage/Stability

Store at 15°C to 30°C (59°F to 86°F).

Medication Patient Education with HCAHPS Considerations

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience fatigue, nausea, vomiting, cough, or shivering. Have patient report immediately to prescriber signs of high potassium (abnormal heartbeat, confusion, dizziness, passing out, weakness, shortness of breath, or numbness or tingling feeling), signs of kidney problems (unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin), signs of malignant hyperthermia (fast heartbeat, fast breathing, fever, spasm of jaw muscles, or stiffness of jaw muscles), severe dizziness, passing out, difficulty breathing, slow breathing, shallow breathing, abnormal heartbeat, fast heartbeat, slow heartbeat, seizures, stiff muscles, blue/gray skin discoloration, or agitation (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Medication Safety Issues

Sound-alike/look-alike issues:

High alert medication:

Contraindications

Hypersensitivity to sevoflurane, other halogenated anesthetics, or any component of the formulation; known or suspected 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).

• Hepatic effects: Postoperative hepatitis or hepatic dysfunction with or without jaundice has rarely 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. Use is contraindicated in patients susceptible to malignant hyperthermia such as those with certain inherited ryanodine receptor mutations.

• 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: Causes dose-dependent respiratory depression and blunted ventilatory response to hypoxia and hypercapnia (Golembiewski 2004). 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.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

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).

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).

Breast-Feeding Considerations

It is not known if sevoflurane is present in breast milk; however, due to rapid washout, sevoflurane levels in breast milk are likely of no clinical importance 24 hours after anesthesia.

The Academy of Breast Feeding 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]).

Briggs' Drugs in Pregnancy & Lactation

• Sevoflurane

Adverse Reactions

>10%:

Cardiovascular: Hypotension (4% to 11%; dose-dependent)

Central nervous system: Agitation (7% to 15%)

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

Respiratory: Cough (5% to 11%)

1% to 10%:

Cardiovascular: Tachycardia (2% to 6%), bradycardia (5%), hypertension (2%)

Central nervous system: Drowsiness (9%), shivering (6%), dizziness (4%), headache (1%), hypothermia (1%), myoclonus (1%), delirium (emergence)

Gastrointestinal: Sialorrhea (2% to 4%)

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

Miscellaneous: Fever (1%)

<1%, postmarketing, and/or case reports: Acidosis, albuminuria, amblyopia, anaphylactoid reaction, anaphylaxis, atrial arrhythmia, atrial fibrillation, bigeminy, bronchospasm, cardiac arrhythmia, chest discomfort, complete atrioventricular block, confusion, conjunctivitis, crying, depression of ST segment on ECG, dysgeusia, dyspnea, extrasystoles (supraventricular), facial edema, glycosuria, hemorrhage, hepatic failure, hepatic insufficiency, hepatic necrosis, hepatitis, hepatotoxicity (idiosyncratic; Chalasani 2014), hiccups, hyperbilirubinemia, hyperglycemia, hypersensitivity reaction, hyperkalemia (pediatric patients; postoperative), hypertonia, hyperventilation, hypophosphatemia, hypoventilation, hypoxia, increased blood urea nitrogen, increased bronchial secretions, increased creatine phosphokinase, increased lactate dehydrogenase, increased liver enzymes (transient), increased serum alkaline phosphatase, increased serum ALT, increased serum AST, increased serum creatinine, increased serum glucose (transient), insomnia, inversion T wave on ECG, jaundice, leukocytosis (may be transient), malignant hyperthermia, myoglobinuria, nervousness, oliguria, pain, pharyngitis, pruritus, second degree atrioventricular block, seizure (rare), skin rash, stridor, syncope, thrombocytopenia, tooth enamel damage (fluorosis), urinary retention, urticaria, ventricular premature contractions, weakness, wheezing, xerostomia

Allergy and Idiosyncratic Reactions

• Inhalational Anesthetic Allergy

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 Open Interactions

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 amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Risk D: Consider therapy modification

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

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). 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. 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. 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

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

Cannabis: May enhance the CNS depressant effect of CNS Depressants. 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

Dexmethylphenidate: 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

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

DOPamine: Inhalational Anesthetics may enhance the arrhythmogenic effect of DOPamine. Management: Avoid use of dopamine in patients receiving halogenated hydrocarbon anesthetics. If concomitant treatment cannot be avoided, monitor for arrhythmia. Dopamine induced ventricular arrhythmia may be reversible with propranolol based on animal data. Risk X: Avoid combination

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

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. 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. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. 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

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Risk D: Consider therapy modification

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

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

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

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

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

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

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. 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

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification

Methylphenidate: May enhance the hypertensive effect of Inhalational Anesthetics. Risk D: Consider therapy modification

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

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

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

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

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

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. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Risk D: Consider therapy modification

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

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

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

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest 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

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

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Risk D: Consider therapy modification

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

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

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

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

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

Gene Testing May Be Considered

• CACNA1S - Sevoflurane
• RYR1 - Sevoflurane

Genes of Interest

• Cytochrome P450 2E1

Monitoring Parameters

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

Dosage Forms: US

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

Solution, Inhalation:

Sojourn: (250 mL [DSC]) [additive free]

Ultane: (250 mL)

Generic: (100 mL, 250 mL)

Anatomic Therapeutic Chemical (ATC) Classification

• N01AB08

Generic Available (US)

Yes

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.

Pharmacodynamics/Kinetics

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

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

No significant effects or complications reported

Effects on Bleeding

No information available to require special precautions

Related Information

• Drugs With Actionable Pharmacogenomic Recommendations
• Malignant Hyperthermia

FDA Approval Date

June 07, 1995

References

American College of Obstetricians and Gynecologists (ACOG). ACOG practice bulletin no. 209: obstetric analgesia and anesthesia. Obstet Gynecol. 2019;133(3):e208-e225.[PubMed 30801474]

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Brand Names: International

Amasevo (EG); Floves (CR, DO, GT, HN, NI, PA, SV); Haluran (SA); Sefether (TH); Sevo (PH, TH); Sevocris (PY); Sevodex (ID); Sevofran (KR); Sevofrane (CN, JP); Sevoran (BD, LU, LV, RU); Sevorane (AR, AT, AU, BE, BG, BO, BR, CH, CL, CO, CY, CZ, DE, DK, EC, EE, ES, FI, FR, GR, HK, HR, HU, ID, IE, IL, IS, IT, KR, LK, LT, MX, MY, NL, NO, NZ, PE, PH, PK, PL, PR, PT, PY, RO, SE, SG, SI, SK, TH, TR, UY, VE, VN); Sevotan (EG); Sojourn (ID, IL, LB, PH, SA, SG, TH); Sovener (CR, DO, GT, HN, NI, PA, SV); Ultane (TW, ZW)

Last Updated 3/20/20