Sevoflurane

Sevoflurane
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chetan Lokhande, M.B.B.S [2]

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Overview

Sevoflurane is a general anesthetic that is FDA approved for the {{{indicationType}}} of general anesthesia. Common adverse reactions include cardiovascular: bradyarrhythmia (3% to 5% ), hypotension (4% to 11% ), gastrointestinal: nausea (25% ), vomiting (18% ), neurologic: somnolence (9% ), psychiatric: agitation (6% to 15%), respiratory: cough (5% to 11% ), interrupted breathing (2% to 6% ), other: shivering (6% ).

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

• General anesthesia: 0.5% to 3% concentration with or without concomitant use of nitrous oxide

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information about Off-Label Guideline-Supported Use of Sevoflurane in adult patients.

Non–Guideline-Supported Use

There is limited information about Off-Label Non–Guideline-Supported Use of Sevoflurane in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

• General anesthesia: 0.5% to 3% concentration with or without concomitant use of nitrous oxide

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information about Off-Label Guideline-Supported Use of Sevoflurane in pediatric patients.

Non–Guideline-Supported Use

There is limited information about Off-Label Non–Guideline-Supported Use of Sevoflurane in pediatric patients.

Contraindications

Sevoflurane can cause malignant hyperthermia. It should not be used in patients with known sensitivity to sevoflurane or to other halogenated agents nor in patients with known or suspected susceptibility to malignant hyperthermia.

Warnings

Although data from controlled clinical studies at low flow rates are limited, findings taken from patient and animal studies suggest that there is a potential for renal injury which is presumed due to Compound A. Animal and human studies demonstrate that sevoflurane administered for more than 2 MAC·hours and at fresh gas flow rates of < 2 L/min may be associated with proteinuria and glycosuria.

While a level of Compound A exposure at which clinical nephrotoxicity might be expected to occur has not been established, it is prudent to consider all of the factors leading to Compound A exposure in humans, especially duration of exposure, fresh gas flow rate, and concentration of sevoflurane. During sevoflurane anesthesia the clinician should adjust inspired concentration and fresh gas flow rate to minimize exposure to Compound A. To minimize exposure to Compound A, sevoflurane exposure should not exceed 2 MAC·hours at flow rates of 1 to < 2 L/min. Fresh gas flow rates < 1 L/min are not recommended.

Because clinical experience in administering sevoflurane to patients with renal insufficiency (creatinine > 1.5 mg/dL) is limited, its safety in these patients has not been established.

Sevoflurane may be associated with glycosuria and proteinuria when used for long procedures at low flow rates. The safety of low flow sevoflurane on renal function was evaluated in patients with normal preoperative renal function. One study compared sevoflurane (N = 98) to an active control (N = 90) administered for ≥ 2 hours at a fresh gas flow rate of ≤ 1 Liter/minute. Per study defined criteria (Hou et al.) one patient in the sevoflurane group developed elevations of creatinine, in addition to glycosuria and proteinuria. This patient received sevoflurane at fresh gas flow rates of ≤ 800 mL/minute. Using these same criteria, there were no patients in the active control group who developed treatment emergent elevations in serum creatinine.

Sevoflurane may present an increased risk in patients with known sensitivity to volatile halogenated anesthetic agents. KOH containing CO2 absorbents are not recommended for use with sevoflurane.

Reports of QT prolongation, associated with torsade de pointes (in exceptional cases, fatal), have been received. Caution should be exercised when administering sevoflurane to susceptible patients (e.g. patients with congenital Long QT Syndrome or patients taking drugs that can prolong the QT interval).

Malignant Hyperthermia

In susceptible individuals, potent inhalation anesthetic agents, including sevoflurane, may trigger a skeletal muscle hypermetabolic state leading to high oxygen demand and the clinical syndrome known as malignant hyperthermia. Sevoflurane can induce malignant hyperthermia in genetically susceptible individuals, such as those with certain inherited ryanodine receptor mutations. The clinical syndrome is signaled by hypercapnia, and may include muscle rigidity, tachycardia, tachypnea, cyanosis, arrhythmias, and/or unstable blood pressure. Some of these nonspecific signs may also appear during light anesthesia, acute hypoxia, hypercapnia, and hypovolemia.

In clinical trials, one case of malignant hyperthermia was reported. In addition, there have been postmarketing reports of malignant hyperthermia. Some of these cases have been fatal.

Treatment of malignant hyperthermia includes discontinuation of triggering agents (e.g., sevoflurane), administration of intravenous dantrolene sodium (consult prescribing information for intravenous dantrolene sodium for additional information on patient management), and application of supportive therapy. Supportive therapy may include efforts to restore body temperature, respiratory and circulatory support as indicated, and management of electrolyte-fluid-acid-base abnormalities. Renal failure may appear later, and urine flow should be monitored and sustained if possible.

Perioperative Hyperkalemia

Use of inhaled anesthetic agents has been associated with rare increases in serum potassium levels that have resulted in cardiac arrhythmias and death in pediatric patients during the postoperative period. Patients with latent as well as overt neuromuscular disease, particularly Duchenne muscular dystrophy, appear to be most vulnerable. Concomitant use of succinylcholine has been associated with most, but not all, of these cases. These patients also experienced significant elevations in serum creatine kinase levels and, in some cases, changes in urine consistent with myoglobinuria. Despite the similarity in presentation to malignant hyperthermia, none of these patients exhibited signs or symptoms of muscle rigidity or hypermetabolic state. Early and aggressive intervention to treat the hyperkalemia and resistant arrhythmias is recommended; as is subsequent evaluation for latent neuromuscular disease.

Adverse Reactions

Clinical Trials Experience

Adverse events are derived from controlled clinical trials conducted in the United States, Canada, and Europe. The reference drugs were isoflurane, enflurane, and propofol in adults and halothane in pediatric patients. The studies were conducted using a variety of premedications, other anesthetics, and surgical procedures of varying length. Most adverse events reported were mild and transient, and may reflect the surgical procedures, patient characteristics (including disease) and/or medications administered.

Of the 5182 patients enrolled in the clinical trials, 2906 were exposed to sevoflurane, including 118 adults and 507 pediatric patients who underwent mask induction. Each patient was counted once for each type of adverse event. Adverse events reported in patients in clinical trials and considered to be possibly or probably related to sevoflurane are presented within each body system in order of decreasing frequency in the following listings. One case of malignant hyperthermia was reported in pre-registration clinical trials.

Adverse Events During the Induction Period (from Onset of Anesthesia by Mask Induction to Surgical Incision) Incidence > 1%

Adult Patients (N = 118)

Cardiovascular

Bradycardia 5%, Hypotension 4%, Tachycardia 2%

Nervous System

Agitation 7%

Respiratory System

Laryngospasm 8%, Airway obstruction 8%, Breathholding 5%, Cough Increased 5%

Pediatric Patients (N = 507)

Cardiovascular

Tachycardia 6%, Hypotension 4%

Nervous System

Agitation 15%

Respiratory System

Breathholding 5%, Cough Increased 5%, Laryngospasm 3%, Apnea 2%

Digestive System

Increased salivation 2%

Adverse Events During Maintenance and Emergence Periods, Incidence > 1% (N = 2906)

Body as a whole

Fever 1%, Shivering 6%, Hypothermia 1%, Movement 1%, Headache 1%

Cardiovascular

Hypotension 11%, Hypertension 2%, Bradycardia 5%, Tachycardia 2%

Nervous System

Somnolence 9%, Agitation 9%, Dizziness 4%, Increased salivation 4%

Digestive System

Nausea 25%, Vomiting 18%

Respiratory System

Cough increased 11%, Breathholding 2%, Laryngospasm 2%

Adverse Events, All Patients in Clinical Trials (N = 2906), All Anesthetic Periods, Incidence < 1% (Reported in 3 or More Patients)

Body as a whole

Asthenia, Pain

Cardiovascular

Arrhythmia, Ventricular Extrasystoles, Supraventricular Extrasystoles, Complete AV Block, Bigeminy, Hemorrhage, Inverted T Wave, Atrial Fibrillation, Atrial Arrhythmia, Second Degree AV Block, Syncope, S-T Depressed

Nervous System

Crying, Nervousness, Confusion, Hypertonia, Dry Mouth, Insomnia

Respiratory System

Sputum Increased, Apnea, Hypoxia, Wheezing, Bronchospasm, Hyperventilation, Pharyngitis, Hiccup, Hypoventilation, Dyspnea, Stridor

Metabolism and Nutrition

Increases in LDH, AST, ALT, BUN, Alkaline Phosphatase, Creatinine, Bilirubinemia, Glycosuria, Fluorosis, Albuminuria, Hypophosphatemia, Acidosis, Hyperglycemia

Hemic and Lymphatic System

Leucocytosis, Thrombocytopenia

Skin and Special Senses

Amblyopia, Pruritus, Taste Perversion, Rash, Conjunctivitis

Urogenital

Urination Impaired, Urine Abnormality, Urinary Retention, Oliguria

See WARNINGS for information regarding malignant hyperthermia.

Postmarketing Experience

The following adverse events have been identified during post-approval use of Ultane (sevoflurane USP). Due to the spontaneous nature of these reports, the actual incidence and relationship of Ultane to these events cannot be established with certainty.

CNS

Seizures — Post-marketing reports indicate that sevoflurane use has been associated with seizures. The majority of cases were in children and young adults, most of whom had no medical history of seizures. Several cases reported no concomitant medications, and at least one case was confirmed by EEG. Although many cases were single seizures that resolved spontaneously or after treatment, cases of multiple seizures have also been reported. Seizures have occurred during, or soon after sevoflurane induction, during emergence, and during post-operative recovery up to a day following anesthesia.

Cardiac

Cardiac arrest

Hepatic

   Cases of mild, moderate and severe post-operative hepatic dysfunction or hepatitis with or without jaundice have been reported. Histological evidence was not provided for any of the reported hepatitis cases. In most of these cases, patients had underlying hepatic conditions or were under treatment with drugs known to cause hepatic dysfunction. Most of the reported events were transient and resolved spontaneously (see PRECAUTIONS).
   Hepatic necrosis
   Hepatic failure

Other

   Malignant hyperthermia (see CONTRAINDICATIONS and WARNINGS)
   Allergic reactions, such as rash, urticaria, pruritus, bronchospasm, anaphylactic or anaphylactoid reactions (see CONTRAINDICATIONS)
   Reports of hypersensitivity (including contact dermatitis, rash, dyspnea, wheezing, chest discomfort, swelling face, or anaphylactic reaction) have been received, particularly in association with long-term occupational exposure to inhaled anesthetic agents, including sevoflurane (see OCCUPATIONAL CAUTION).

Laboratory Findings

   Transient elevations in glucose, liver function tests, and white blood cell count may occur as with use of other anesthetic agents.

Drug Interactions

There is limited information regarding Sevoflurane Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Sevoflurane in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Sevoflurane in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Sevoflurane during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Sevoflurane in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Sevoflurane in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Sevoflurane in geriatric settings.

Gender

There is no FDA guidance on the use of Sevoflurane with respect to specific gender populations.

Race

There is no FDA guidance on the use of Sevoflurane with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Sevoflurane in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Sevoflurane in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Sevoflurane in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Sevoflurane in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Sevoflurane Administration in the drug label.

Monitoring

There is limited information regarding Sevoflurane Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Sevoflurane and IV administrations.

Overdosage

There is limited information regarding Sevoflurane overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

Mechanism of Action

There is limited information regarding Sevoflurane Mechanism of Action in the drug label.

Structure

There is limited information regarding Sevoflurane Structure in the drug label.

Pharmacodynamics

There is limited information regarding Sevoflurane Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Sevoflurane Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Sevoflurane Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Sevoflurane Clinical Studies in the drug label.

How Supplied

There is limited information regarding Sevoflurane How Supplied in the drug label.

Storage

There is limited information regarding Sevoflurane Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Sevoflurane Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Sevoflurane interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Sevoflurane Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Sevoflurane Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.