Regulatory Decision Summary for Bridion
Review decision
The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.
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What was the purpose of this submission?
This Supplement to a New Drug Submission (SNDS) was filed as a Response to a Notice of Deficiency (NOD-R) to expand the indication to pediatric patients (≥ 2 years of age) and incorporate various changes to the Canadian Product Monograph (PM), related to this extension. The PM was also updated according to the 2020 PM template.
Why was the decision issued?
In addition to previously submitted studies, among which was a limited pediatric trial considered adequate to support efficacy but not safety, this Response to a Notice of Deficiency (NOD-R) included a Phase 4, double-blinded, randomized, active comparator-controlled trial in 272 pediatric participants.
Based on the clinical studies submitted by the sponsor, Bridion reversed neuromuscular blockade by rocuronium or vecuronium in a faster and more predictable manner than the reversal agent, neostigmine. Children and adolescents (2 to < 17 years) took a mean of 2.1 minutes with Bridion, versus 10.4 minutes with neostigmine, for reversal of moderate neuromuscular blockade. In general, faster reversal times are associated with a better prognosis and shorter stays in the pediatric intensive care unit (PICU). Bridion was also capable of reversing deeper neuromuscular blockade, for which there are currently no available options for pediatric patients.
Bridion was well-tolerated in pediatric patients, with a safety profile similar to that observed with adults. No new adverse reactions were observed following administration in children or adolescents (2 to < 17 years of age). The same safety concerns associated with the use of Bridion in adults were observed in children. The most common adverse reactions included vomiting, pain, nausea, hypotension, and headache.
Despite the above similarities, a difference was noted in the incidence of bradycardia. In adult clinical trials, the incidence of bradycardia following reversal of moderate neuromuscular blockade by Bridion was 1%, compared to 10% reported in pediatric clinical studies.
Uncertainties were noted. Although Bridion is known to cause anaphylaxis and hypersensitivity (black box warning), no adjudicated cases were reported in pediatric trials. However, the subject numbers in the studies provided by the sponsor may be too low for an accurate assessment. Also, the dose of 16 mg/kg recommended for urgent/immediate reversal of neuromuscular blockade in adults was not studied in pediatric subjects. Lastly, data were not provided to direct appropriate dosing in morbidly obese pediatric patients.
All identified risks and uncertainties were appropriately addressed through labelling.
Overall, the benefit-harm-uncertainty profile for Bridion remains favourable for both adults and pediatrics (2-17 years of age).
Decision issued
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations