SEVORANE AF

1 Dosing Considerations Fresh gas flow rates of less than 2 L/min in a circle absorber system are not recommended, as safety at lower rates has not yet been established: The concentration of SEVORANE AF (sevoflurane) being delivered from a vaporizer during anesthesia should be known.

This may be accomplished by using a vaporizer calibrated specifically for SEVORANE AF. The administration of general anesthesia must be individualized based on the patient's response.

Pre-Anesthetic Medication:

No specific premedication is either indicated or contraindicated with SEVORANE AF. The decision as to whether or not to premedicate and the choice of premedication is left to the discretion of the anesthesiologist.

Induction:

SEVORANE AF has a non-pungent odour and does not cause respiratory irritability; therefore, it is suitable for mask induction in pediatrics and adults. 5 to 3% SEVORANE AF with or without the concomitant use of nitrous oxide. , those identified as contraindicated).

Table 6. SEVORANE AF can be administered with any type of anesthesia circuit. 2 Recommended Dose and Dosage Adjustment Minimum alveolar concentration (MAC) values according to age are presented in Table 1Table 1. 3%.

Note 2:

In 1 to < 3 year old pediatric patients, 60% N2O / 40% O2 was used. 4 Administration SEVORANE AF should be administered only by persons trained in the administration of general anesthesia. See 7 WARNINGS AND PRECAUTIONS, General. SEVORANE AF (sevoflurane) Product Monograph Page 6 of 34

1 Adverse Reaction Overview 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.

Nausea, vomiting, and delirium have been observed in the post-operative period, common sequelae of surgery and general anesthesia, which may be due to inhalational anesthetic, other agents administered intra-operatively or post-operatively, and to the patient's response to the surgical procedure.

2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use. Of the 5182 patients enrolled in the clinical trials, 2906 were exposed to SEVORANE AF (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 are presented within each body system in Table 3, Table 4 and Table 5. One case of malignant hyperthermia was reported in pre-registration clinical trials.

SEVORANE AF (sevoflurane) Product Monograph Page 12 of 34 Table 3 - Adverse Events During Induction Period (From Onset of Anesthesia by Mask Induction to Surgical Incision) Possibly or Probably Related with Incidence > 1% Body System Adult Patients N = 118 (%) Pediatric Patients N = 507 (%) Cardiovascular Bradycardia 5 - Hypotension 4 4 Tachycardia 2 6 Nervous System Agitation 7 15 Increased salivation - 2 Respiratory System Airway obstruction 8 - Apnea - 2 Breath-holding 5 5 Cough increased 5 5 Laryngospasm 8 3 NOTE: Similar incidence of adverse events was noted when all adverse reactions were recorded, not only possibly or probably related.

3 Pediatrics 05/2021 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. RECENT MAJOR LABEL CHANGES ........................................................................................................

2 TABLE OF CONTENTS .......................................................................................................................... 2 PART I: HEALTH PROFESSIONAL INFORMATION ..................................................................................

4 1 INDICATIONS ......................................................................................................................... 1 Pediatrics ...............................................................................................................................

2 Geriatrics ............................................................................................................................... 4 2 CONTRAINDICATIONS ............................................................................................................

4 3 SERIOUS WARNINGS AND PRECAUTIONS BOX ........................................................................ 4 4 DOSAGE AND ADMINISTRATION ............................................................................................

1 Dosing Considerations .......................................................................................................... 2 Recommended Dose and Dosage Adjustment .....................................................................

4 Administration ...................................................................................................................... 5 5 OVERDOSAGE ........................................................................................................................

 SEVORANE AF (sevoflurane) is contraindicated in patients with known sensitivity to sevoflurane or to other halogenated inhalation anesthetics.  SEVORANE AF is contraindicated in patients in whom liver dysfunction, jaundice or unexplained fever, leucocytosis, or eosinophilia has occurred after a previous halogenated anesthetic administration.

See 7 WARNINGS AND PRECAUTIONS, Hepatic/Biliary/Pancreatic.  SEVORANE AF is contraindicated in patients with known or suspected genetic susceptibility to malignant hyperthermia, or in patients with a known or suspected history of malignant hyperthermia.

 SEVORANE AF should not be used when general anesthesia is contraindicated.