Prescription Drug Information: Sevoflurane (Page 3 of 3)
ADVERSE REACTIONS
Clinical Trials Experience
Adverse events are derived from controlled clinical studies 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 studies, 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 studies 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 studies.
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 Studies (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 sevoflurane. Due to the spontaneous nature of these reports, the actual incidence and relationship of sevoflurane to these events cannot be established with certainty.
Central Nervous System
• 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.
• Delirium
Cardiac
• Cardiac arrest
• QT prolongation associated with Torsade de Pointe
• Bradycardia in patients with Down syndrome
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, WARNINGS)
• Allergic reactions, such as rash, urticaria, pruritus, bronchospasm, and anaphylactic 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 SAFETY AND HANDLING — 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.
OVERDOSAGE
In the event of overdosage, or what may appear to be overdosage, the following action should be taken: discontinue administration of sevoflurane, maintain a patent airway, initiate assisted or controlled ventilation with oxygen, and maintain adequate cardiovascular function.
DOSAGE AND ADMINISTRATION
The concentration of sevoflurane being delivered from a vaporizer should be known. This may be accomplished by using a vaporizer calibrated specifically for sevoflurane. The administration of general anesthesia must be individualized based on the patient’s response.
Replacement of Desiccated CO 2 Absorbents
When a clinician suspects that the CO 2 absorbent may be desiccated, it should be replaced. The exothermic reaction that occurs with sevoflurane and CO 2 absorbents is increased when the CO 2 absorbent becomes desiccated, such as after an extended period of dry gas flow through the CO 2 absorbent canisters (see PRECAUTIONS).
Pre-anesthetic Medication
No specific premedication is either indicated or contraindicated with sevoflurane. The decision as to whether or not to premedicate and the choice of premedication is left to the discretion of the anesthesiologist.
Induction
Sevoflurane has a nonpungent odor and does not cause respiratory irritability; it is suitable for mask induction in pediatrics and adults.
Maintenance
Surgical levels of anesthesia can usually be achieved with concentrations of 0.5 — 3% sevoflurane with or without the concomitant use of nitrous oxide. Sevoflurane can be administered with any type of anesthesia circuit.
Table 9. MAC Values for Adults and Pediatric Patients According to Age
| Age of Patient (years) | Sevoflurane in Oxygen | Sevoflurane in 65% N 2 O/35% O 2 |
| 0 — 1 months # | 3.3% | |
| 1 — < 6 months | 3.0% | |
| 6 months — < 3 years | 2.8% | 2.0%@ |
| 3 — 12 | 2.5% | |
| 25 | 2.6% | 1.4% |
| 40 | 2.1% | 1.1% |
| 60 | 1.7% | 0.9% |
| 80 | 1.4% | 0.7% |
# Neonates are full-term gestational age. MAC in premature infants has not been determined.
@ In 1 — < 3 year old pediatric patients, 60% N 2 O/40% O 2 was used.
HOW SUPPLIED
Sevoflurane, USP, Volatile Liquid for Inhalation, is packaged in amber colored bottles containing 250 mL Sevoflurane, USP, NDC # 66794-022-25.
SAFETY AND HANDLING
Occupational Caution
There is no specific work exposure limit established for sevoflurane. However, the National Institute for Occupational Safety and Health 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 N 2 O) (see ADVERSE REACTIONS).
Storage
Store at controlled room temperature, 15° — 30°C (59° — 86°F). See USP.
ANIMAL TOXICOLOGY AND/OR PHARMACOLOGY
Published studies in animals demonstrate that the use of anesthetic agents during the period of rapid brain growth or synaptogenesis results in widespread neuronal and oligodendrocyte cell loss in the developing brain and alterations in synaptic morphology and neurogenesis. Based on comparisons across species, the window of vulnerability to these changes is believed to correlate with exposures in the third trimester through the first several months of life, but may extend out to approximately 3 years of age in humans.
In primates, exposure to 3 hours of an anesthetic regimen that produced a light surgical plane of anesthesia did not increase neuronal cell loss; however, treatment regimens of 5 hours or longer increased neuronal cell loss. Data in rodents and in primates suggest that the neuronal and oligodendrocyte cell losses are associated with subtle but prolonged cognitive deficits in learning and memory. The clinical significance of these nonclinical findings is not known, and healthcare providers should balance the benefits of appropriate anesthesia in pregnant women, neonates and young children who require procedures against the potential risks suggested by the nonclinical data (see WARNINGS — Pediatric Neurotoxicity, PRECAUTIONS — Pregnancy, PRECAUTIONS — Pediatric Use).
Manufactured by:
Piramal Critical Care, Inc.
3950 Schelden Circle
Bethlehem, PA 18017
(888) 822-8431
Last Revised: May 2022
© 2022 Piramal Critical Care, Inc.
| SEVOFLURANE sevoflurane liquid | |||||||||||||
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| Labeler — Piramal Critical Care Inc (805600439) |
| Establishment | |||
| Name | Address | ID/FEI | Operations |
| Piramal Critical Care Inc | 805600439 | analysis (66794-022), api manufacture (66794-022), label (66794-022), manufacture (66794-022), pack (66794-022) | |
Revised: 06/2022 Piramal Critical Care Inc
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