Suzetrigine Versus Tramadol for Acute Postoperative Pain: Systematic Review and Meta-Analysis

Abstract

Opioids remain the backbone for postoperative analgesia, but adverse effects and misuse remain major concerns. Suzetrigine (VX-548), a selective NaV1.8 inhibitor, is an FDA-approved non-opioid analgesic for moderate-to-severe acute pain. This PRISMA-guided systematic review and meta-analysis evaluated the efficacy and adverse effects of suzetrigine versus tramadol following bunionectomy or abdominoplasty. PubMed, Scopus, Cochrane CENTRAL, Ovid, ClinicalTrials.gov, and medRxiv were searched. Six randomized clinical trials involving 2,136 participants (1,289 treatment; 847 placebo) were included. Placebo-adjusted treatment effects were compared using random-effects meta-regression with placebo as the common comparator. Suzetrigine was associated with significantly lower SPID24 than intravenous tramadol after adjustment for surgery type (β = −7.46; 95% CI, −12.52 to −2.40; p = 0.0184), indicating greater analgesic efficacy with tramadol at 24 hours. No significant difference was observed at 48 hours (β = −2.49; 95% CI, −24.83 to 19.84; p = 0.75). Suzetrigine demonstrated significantly lower odds of nausea (p = 0.003) and vomiting (p = 0.010) than tramadol, with no significant differences in constipation or headache. GRADE assessment determined the certainty of evidence to be very low for the efficacy outcomes, constipation, and headache, and low for nausea and vomiting. Direct comparative trials are necessary to confirm suzetrigine’s relative efficacy and adverse-effect profile versus tramadol.