Adverse reactions : תופעות לוואי

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.

Post-Marketing Experience
The following adverse events have been identified during post-approval use of SOJOURN SEVOFLURANE USP (sevoflurane USP). Due to the spontaneous nature of these reports, the actual incidence and relationship of SOJOURN SEVOFLURANE USP 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 postoperative 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.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form: https://sideeffects.health.gov.il