BACKGROUND: The ongoing opioid epidemic underscores the urgent need for effective nonopioid options for acute pain management. Suzetrigine, a selective voltage-gated sodium channel NaV1.8 inhibitor, represents a mechanistically novel analgesic targeting peripheral nociception and may reduce reliance on opioid therapy. It received FDA approval on January 30, 2025, for the treatment of moderate-to-severe acute pain in adults. This evidence-based review evaluates the efficacy and safety of suzetrigine as an opioid-sparing option for outpatient acute pain management.
METHODS: A structured literature search of PubMed was conducted from database inception through January 2026 using the terms “suzetrigine” and “NaV1.8.” Eligible studies were randomized, double-blind, controlled trials enrolling adults (≥18 years) with moderate-to-severe acute pain (numeric pain rating scale ≥4) treated with suzetrigine and reporting validated pain outcomes. Phase 1 pharmacokinetic studies without efficacy endpoints were excluded.
RESULTS: One randomized controlled trial publication met inclusion criteria, reporting outcomes from two phase 3 trials involving patients undergoing abdominoplasty (n=1,118) and bunionectomy (n=1,073). In both trials, suzetrigine administered as a 100-mg loading dose followed by 50 mg every 12 hours produced statistically and clinically significant reductions in pain intensity compared with placebo over 48 hours, measured by the time-weighted sum of pain intensity difference (SPID48). Adjusted mean treatment effects favored suzetrigine by 48.4 points in the abdominoplasty trial (95% CI 33.6–63.1; P
CONCLUSION: Current evidence suggests that suzetrigine provides effective analgesia comparable to opioid therapy for acute postoperative pain, with a more favorable safety and tolerability profile. These findings support its potential role as an opioid-sparing option in outpatient acute pain management. However, available evidence is limited to short-term postoperative settings in relatively healthy adults. Further studies are needed to evaluate its effectiveness in nonsurgical acute pain conditions, broader patient populations, and real-world opioid-sparing outcomes.