Efficacy and Safety of Suzetrigine for Acute Postoperative Pain: A GRADE Assessed Systematic Review and Meta-Analysis

Suzetrigine represents a novel non-opioid option for managing acute postoperative pain. Management of this pain often relies on traditional analgesics, including opioids, NSAIDs, and acetaminophen, but the use of these agents can be complicated by significant side effects and patient variability in response. This systematic review and meta-analysis aimed to assess the efficacy and safety of suzetrigine compared to placebo in adults with acute postoperative pain. A literature search was conducted across multiple databases from inception to July 25, 2025, which identified randomized controlled trials (RCTs) evaluating suzetrigine or its analog VX-548. Primary outcomes included standardized pain intensity difference at 48 h and incidence of adverse events. Four RCTs involving 2,768 patients undergoing abdominoplasty or bunionectomy were analyzed. Results showed that suzetrigine significantly improved SPID48 scores compared to placebo (mean difference [MD] = 38.76; 95% CI: 28.97-48.54; p < 0.00001) with minimal heterogeneity (I² = 5%). It also reduced the risk of overall AEs (RR = 0.86), nausea (RR = 0.72), and dizziness (RR = 0.57), without increasing serious AEs. No significant differences were observed for constipation, headache, vomiting, or moderate AEs. These findings suggest that suzetrigine offers effective and well-tolerated analgesia, supporting its role in opioid-sparing postoperative pain regimens.