OBJECTIVE To evaluate the efficacy and safety of the novel non-opioid analgesic suzetrigine in patients with moderate-to-severe pain.

METHODS A systematic review of medical databases was conducted from inception until September 2025. All randomized controlled trials(RCTs) evaluating the efficacy and safety of suzetrigine in patients with moderate-to-severe pain were included. Primary outcome measures included 24/48 h period of the time-weighted summed pain intensity difference(SPID) and the reduction rate of resting numeric pain rating scale(NRS) scores within 48 h, as well as the incidence of all adverse events, including nausea, vomiting, et al.

RESULTS A total of 4 RCTs involving 2599 patients were included, and divided into suzetrigine group(n=1009), and control group(n=1590) which treated with hydrocodone bitartrate-acetaminophen(n=1015) or placebo(n=575). The analysis revealed that compared with control groups, suzetrigine significantly reduced SPID24/SPID48 and increased the reduction rate of resting NRS scores within 48 h, with particularly notable efficacy observed in the abdominoplasty. Compared with the placebo group, the analgesic effect of suzetrigine was highly significant and comparable to that of hydrocodone bitartrate-acetaminophen group. The safety profile of suzetrigine was more favorable than that of the control groups, as evidenced by significantly lower risk ratios for all adverse events, nausea, vomiting, and dizziness. However, the long-term efficacy and safety profile remains unclear.

CONCLUSION Suzetrigine is an effective and safe non-opioid analgesic for patients with moderate-to-severe pain, providing rapid analgesia non-inferior to hydrocodone bitartrate-acetaminophen with a favorable safety profile. Nevertheless, due to the limited number of included studies and high heterogeneity, further clinical studies incorporating multidimensional pain management assessments are warranted for validation.