Selective Nav1.8 inhibition by suzetrigine, a novel nonopioid analgesic for acute pain management: A systematic review and metanalysis
Saudi J Anaesth. 2026 Jan 2;20(1):82-91. doi: 10.4103/sja.sja_602_25. eCollection 2026 Jan-Mar.
ABSTRACT
BACKGROUND: Suzetrigine, a novel nonopioid analgesic, selectively inhibits voltage-gated sodium channel 1.8 (NaV1.8) and has recently been approved for the management of moderate to severe acute pain. This meta-analysis aimed to evaluate the efficacy and safety of suzetrigine by cumulating data from available evidence.
METHODS: A literature search was conducted using ClinicalTrials.gov, PubMed, and Cochrane Central Register of Controlled Trials. Five randomized controlled trials (RCTs) were included in the systematic review, with four RCTs in the meta-analysis. The primary efficacy outcomes were time-weighted sum of pain intensity difference over 48 h (SPID 48) and 24 h (SPID 24) between suzetrigine and placebo. Secondary outcomes included proportion of participants achieving ≥30%, ≥50%, and ≥70% reduction in numeric pain rating scale (NPRS) scores at 48 h and safety analysis.
RESULTS: Suzetrigine showed significantly better efficacy versus placebo in reducing pain, with a standard mean difference of 5.55 (95% CI 2.97-8.13, P < 0.00001) for SPID 48 and 5.33 (95% CI 2.50-8.16, P < 0.00001) for SPID 24. Odds of achieving ≥30%, ≥50%, and ≥70% reduction in NPRS scores at 48 h were significantly higher in the suzetrigine group (OR 1.95, 1.74, and 1.81, respectively; all P < 0.00001). Suzetrigine showed comparable efficacy to hydrocodone bitartrate-acetaminophen (HB/APAP) with a better safety profile, showing lower incidence of adverse events and gastrointestinal side effects.
CONCLUSION: Suzetrigine appears to be an effective, well-tolerated option for acute pain management, showing superiority to placebo and comparable efficacy to HB/APAP, with a better safety profile. However, future long-term studies are needed to assess its efficacy and safety in various acute pain settings.
PMID:41710612 | PMC:PMC12912484 | DOI:10.4103/sja.sja_602_25