The Institute for Clinical and Economic Review (ICER) conducted a review of the value and effectiveness of suzetrigine compared to opioid analgesics. Results were based on the use of suzetrigine or hydrocodone 5 mg/acetaminophen 325 mg for one week postoperatively and the assumption that a one-week course of hydrocodone/acetaminophen would result in an excess of 2 in 10,000 cases of opioid use disorder in the subsequent three years. The report found a slight cost benefit to using suzetrigine compared to hydrocodone/acetaminophen therapy alone. Comparisons are not available to hydrocodone/acetaminophen or suzetrigine therapy with rescue medications or suzetrigine compared to non-opioid therapies alone. [1]
A 2025 systematic review and meta-analysis synthesized data from four randomized controlled trials evaluating suzetrigine for perioperative pain management. This analysis involved 2,768 adult patients undergoing various surgical procedures, with 1,179 patients receiving suzetrigine, an inhibitor of the Nav 1.8 sodium channel, recently approved by the US FDA. The trials compared suzetrigine against both placebo and a standard analgesic regimen comprising hydrocodone with paracetamol. The primary outcome measured was the Summed Pain Intensity Difference over a 48-hour period (SPID-48). This outcome was gauged using a numeric rating scale to assess pain relief over time, comparing initial pain scores to subsequent ratings. The meta-analysis showed that suzetrigine was significantly more effective in reducing pain compared with placebo, evidenced by a mean difference (MD) of 38.64 and a 95% confidence interval (CI) ranging from 26.96 to 47.32. Although the efficacy of suzetrigine did not differ statistically from hydrocodone with paracetamol (MD of 5.27; 95% CI -15.03, 25.57), its safety profile was favorable, with reduced general adverse events (risk ratio 0.83; 95% CI: 0.76, 0.90) and no significant increase in severe adverse events. Notably, significant analgesic benefits were observed in patients undergoing abdominoplasty, suggesting that suzetrigine might be a promising nonopioid alternative for effective perioperative pain relief without the adverse effects associated with opioid-based treatments. However, the authors noted limitations, including potential bias due to industry sponsorship, and highlighted the necessity for further research to confirm these findings across broader populations. [2]
Yet despite showing statistical significance, the results for clinical efficacy between suzetrigine and comparators remained ambiguous due to the use of a non-standardized active comparator, acetaminophen-hydrocodone, which failed to outperform placebo, according to a 2025 editorial. Additionally, only the high dose of suzetrigine demonstrated superiority over placebo. Outcomes were also limited to only a 48-hour post-operative period. Bunionectomy and abdominoplasty were the only prominently studied surgical contexts; thus, efficacy of suzetrigine for more invasive procedures such as large joint arthroplasty and spine surgeries was notably lacking. Overall, the author argues the limited scope of the evaluated surgeries and short follow-up duration bring into question the generalizability of the findings for broader surgical contexts and chronic pain scenarios. Continued postmarket surveillance will be needed to ensure suzetrigine’s safety and efficacy over time, advocating for a balanced regulatory approach that weighs public health imperatives against the rigor of scientific evidence, especially in the quest to find reliable non-opioid analgesics amidst the ongoing opioid crisis. [3]
A 2026 Tactical Combat Casualty Care (TCCC) guideline change article reviewed battlefield analgesia literature and proposed incorporating suzetrigine into the Combat Wound Medication Pack for casualties who remain mission capable, alongside acetaminophen and meloxicam. The proposed suzetrigine regimen was 100 mg orally once, followed by 50 mg every 12 hours. The authors noted that its 2 to 3-hour onset limits use at the point of injury but described a potential role in prolonged casualty care. Regarding safety, the article stated that phase IV data were limited because of suzetrigine’s recent approval and reported minimal adverse effects in 1% to 10% of patients, without treatment discontinuation, sedation, or respiratory depression; however it did not present an original postmarketing surveillance analysis. [4]
A 2026 systematic review and meta-analysis synthesized data from 5 RCTs (N= 2,855) to evaluate the safety and efficacy of suzetrigine for acute moderate-to-severe pain in adults. The primary outcome assessed was treatment-emergent adverse events (TEAEs), while the secondary endpoint was analgesic efficacy measured as the Sum of Pain Intensity Differences over 48 hours (SPID48), as well as reductions in the Numeric Pain Rating Scale (NPRS). The results of the analysis demonstrated that suzetrigine was associated with a significantly lower number of adverse events compared to placebo (risk ratio [RR] 0.86 [95% CI 0.77 to 0.96]) and active comparator hydrocodone.bitartrate/acetaminophen (HB/APAP) (RR 0.81 [95% CI 0.74 to 0.89), with negligible heterogeneity across studies. Specific adverse events that led to treatment discontinuation were significantly less frequent with suzetrigine compared to placebo (nausea: RR 0.72; dizziness: RR 0.57) and HB/APAP (nausea: RR 0.58; vomiting: RR 0.42). The incidence of serious adverse events did not differ significantly among the treatment groups. Regarding efficacy, suzetrigine significantly improved SPID48 scores compared with placebo (standard mean difference [SMD] 0.42 [95% CI 0.31 to 0.53]), indicating a beneficial effect on postoperative pain. However, the differences versus HB/APAP were not statistically significant and were associated with substantial heterogeneity (SMD 0.06 [95% CI -0.17 to 0.29]). NPRS reductions showed no consistent evidence of superiority over control treatments. Overall, these findings suggest that suzetrigine provides effective analgesia for acute moderate-to-severe pain, with a favorable safety profile and potential as a non-opioid alternative to conventional analgesics. [5]
A 2026 systematic review and meta-analysis incorporated 4 randomized datasets from two phase 3 studies (N= 1,584) comparing the efficacy and safety of suzetrigine versus placebo in postoperative pain management of adult patients undergoing abdominoplasty (N= 823) or bunionectomy (N= 761) procedures. The primary efficacy endpoint was pain intensity measured by NPRS at 24 hours postoperatively, with secondary endpoints including NPRS at 48 hours, change-from-baseline pain scores, and incidence of adverse events. Suzetrigine demonstrated modest but statistically significant analgesic effects, reducing pain scores by a mean difference (MD) of −0.93 (95% CI, −1.38 to −0.48; I²= 66.0%) at 24 hours and −1.02 (95% CI, −1.32 to −0.72; I²= 11.8%) at 48 hours compared with placebo. Change-from-baseline analyses corroborated these findings, albeit with less certainty. Additional subgroup analyses by surgery type revealed consistent analgesic benefits across abdominoplasty and bunionectomy cohorts, without significant intergroup differences despite moderate heterogeneity primarily driven by the bunionectomy subgroup (I2= 86.9%). Suzetrigine was also associated with a significantly lower risk of nausea (RR 0.63; 95% CI, 0.42–0.95) and dizziness (RR 0.57; 95% CI, 0.34–0.96), but with no significant differences in headache, vomiting, or constipation. Opioid consumption data were inconsistently reported, precluding conclusions about opioid-sparing effects. Other limitations included the lack of data on serious adverse events and a short duration of follow-up. The authors concluded that additional trials are needed to further characterize suzetrigine’s efficacy and safety profile. [6]
A 2026 letter to the editor describes a single institution's experience with the use of suzetrigine for postoperative pain following orthopedic surgery. Within 6 month following approval by the P&T committee, its use among the initial inpatient cohort found most patients to tolerate therapy, while a minority discontinued due to symptoms potentially treatment-related or due to lack of perceived benefit. However, prescribing may be limited to a dedicaated perioperative pain service due to cost of treatment. Through analgesic stewardship, target populations may be identified while assigning accountable oversight and screening of patients. [7]
A 2026 article published ahead of print describes a phase 4, single-arm, open-label study of suzetrigine used as part of multimodal therapy for acute pain after aesthetic and reconstructive procedures that typically require opioids for at least 72 hours postoperatively. Ninety-nine adults (mean age 41.2 years, 91.9% female, BMI 18–40 kg/m²) received a 100-mg loading dose about one hour before surgery, then 50 mg every 12 hours for up to 14 days or until pain resolved. Other perioperative analgesics were at physician discretion, with around-the-clock acetaminophen plus ibuprofen recommended. The most common procedures were aesthetic breast surgery (33.3%), abdominoplasty with liposuction (28.3%), reconstructive breast revision (13.1%), and turbinoplasty (13.1%). For the primary endpoint, 90.7% of patients (95% CI 83.1–95.7%) rated pain control as good, very good, or excellent on a patient global assessment at the end of treatment, with procedure-specific rates ranging from 76.9% for turbinoplasty to 100% for reconstructive breast surgery and liposuction. Overall, 90.9% of patients needed no rescue opioids from the end of surgery through the end of treatment. The 9 patients who did use them took a mean of 2.4 tablets (20.4 morphine milligram equivalents) over a mean of 2.0 days, and 8 of the 9 started after discharge. Postoperatively, 78.8% used suzetrigine with only acetaminophen and/or ibuprofen and 12.1% used suzetrigine alone, although 98% received opioids before or during surgery. Treatment satisfaction scores were high, at roughly 90 out of 100 across domains, and 67.7% of patients stopped treatment early because their pain resolved. Adverse events occurred in 44.4% of patients, and all were mild or moderate. The most common were nausea (11.1%), elevated creatine phosphokinase (8.1%), and procedural nausea (6.1%); the authors attributed the creatine phosphokinase elevations to extensive muscle dissection during breast augmentation at a single site. Three serious adverse events (bradycardia, pulmonary embolism, and angioedema) were judged unrelated or unlikely related to suzetrigine, and none led to discontinuation. The authors contrast the 90.9% opioid-free rate with published studies of mixed cosmetic procedures, in which fewer than 10% of patients avoided opioids. [8]
In a 2026 hospital quality improvement project aimed at reducing postoperative opioid use by 50%, researchers added preoperative suzetrigine to an existing ERAS protocol (preoperative acetaminophen, celecoxib, and pregabalin; intraoperative liposomal bupivacaine; scheduled postoperative acetaminophen and ibuprofen; oxycodone as needed) for patients undergoing total laparoscopic hysterectomy over a 1-year ambispective study. Among 68 patients, mean postoperative opioid use was significantly lower after the intervention (13.3 mg vs. 28.5 mg oral morphine equivalents, p<0.001). Postintervention patients were five times more likely to decline opioids (p<0.001) without increased pain scores and 24 times more likely to be discharged on the day of surgery (p<0.001). Adding suzetrigine was associated with significant reductions in opioid use and mean pain scores, and the project met its goal of reducing postoperative opioid use by 50%. [9]