ADVERSE REACTIONS
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 pre-medications, 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%, Breath holding 5%, Cough Increased 5%
Pediatric Patients (N = 507)
Cardiovascular: Tachycardia 6%, Hypotension 4%
Nervous System: Agitation 15%
Respiratory System: Breath holding 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%, Breath holding 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.
Post-Marketing Adverse Events:
The following adverse events have been identified during post-approval use of Sevoflurane, USP. Due to the spontaneous nature of these reports, the actual incidence and relationship of Sevoflurane, USP 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, pruritis, bronchospasm, anaphylactic or anaphylactoid reactions (see CONTRAINDICATIONS)
- Rare reports of hypersensitivity (including contact dermatitis, rash, dyspnoea, 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).
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