Regulatory Decision Summary for BRIDION

Pivotal efficacy studies have demonstrated that sugammadex (the medicinal ingredient in Bridion) resulted in a faster reversal of the neuromuscular blockade induced with either vecuronium or rocuronium compared to traditional reversal methods, as measured with a neuromuscular stimulator with a train-of-four (TOF) stimulation pattern.

Sugammadex is associated with various risks in a patient population with a higher health risk (that is [i.e.], surgical patients under general anesthesia), but exposure to these risks is expected to be limited to the operating room or post-anesthesia recovery unit where they can be managed effectively. The tendency for sugammadex to be deposited in the growing bony tissues in children and those in repair in adults is not expected to be a significant risk, considering that sugammadex is intended mainly for single use and repeat use is uncommon. Sugammadex has meaningful effects on the blood coagulation cascades that are detected by changes in coagulation parameters but based on clinical study results this has limited impact on the effective management of patient care even in patients with a high risk of abnormalities in blood coagulation, i.e., no increased bleeding risk with sugammadex 4 mg/kg compared to usual treatment in patients concomitantly treated with an anticoagulant. This information is provided in the product label, and a precaution has been incorporated for monitoring coagulation parameters in patients with known coagulopathies and in patients using anticoagulants who receive a dose of sugammadex higher than 4 mg/kg. Sugammadex was found to have little effect on the cardiac QT interval in patients in a clinical setting where there can be a higher risk of QT prolongation (i.e., associated mainly with the general anesthetics and patients conditions).

The most significant risk associated with sugammadex is hypersensitivity reactions, including anaphylactic reactions, on first exposure and subsequent exposure. The mechanism of these reactions is not clear at this time. This risk has been relatively well characterized in studies in healthy volunteers, but less so in the patient population in clinical anesthesiology. Most of the hypersensitivity reactions seem to require little or no medical intervention. Severe cases, including anaphylactic reactions, seem to respond to standard of care in the post-surgical anesthetic care environment. The Product Monograph (PM) includes a boxed warning and clear language to caution clinicians about this risk.

Sugammadex is indicated for reversal of the effects of rocuronium or vecuronium in adult patients undergoing surgery, with clear instructions of the timing and doses. Use of sugammadex to urgently reverse the effect of an intubation dose of rocuronium is permitted for safety reasons, and clear language describing how it was studied for this purpose in clinical trials has been included in the product label. The waiting times for follow-on use of rocuronium or vecuronium after a sugammadex reversal are also presented in the product label with precautionary language.

Sugammadex may be associated with other risks linked with the peri-operating anesthetic environment, such as the anesthetic requirement to ensure adequate depth of the anesthesia appropriate for the surgical and anesthetic intervention, airway management in patients recovering from the surgery and anesthesia, which are suitable for risk management through labelling and possibly postmarketing risk management tools. These safety issues are not directly linked to sugammadex, but because it is used, it may give false confidence in the use of rocuronium or vecuronium, and other anesthetic practice.

The main benefit that has been demonstrated for sugammadex in clinical trials is faster reversal of the neuromuscular blockade, induced with either vecuronium or rocuronium, than traditional reversal methods in surgical patients receiving general anesthesia. This is communicated adequately in the approved PM and through the clinical use instruction. The identified risks have been adequately addressed in pre-approval nonclinical or clinical studies and risks in clinical use may be adequately managed through the safety warnings and use instruction provided in the PM and its future updates in the postmarketing setting.

Uncertainties remain with regard to the extent to which faster reversal of the neuromuscular blockade translates into a meaningful clinical advantage for patient recovery; why some patients have far slower response to the effect of sugammadex; and, how to improve use of sugammadex in patients with special health conditions. These uncertainties may be resolved in clinical practice and future clinical studies. When used under the recommended conditions of use, provided in the approved Bridion PM, the benefit-harm-uncertainty for this product is considered acceptable at this time.

For more information on Health Canadas decision, please view the Summary Basis of Decision.