Suzetrigine Use After Breast Reconstruction Surgery and Postoperative Outcomes: A Propensity Score–Matched Retrospective Cohort Study (Preprint)

BACKGROUND Suzetrigine, a first-in-class, non-opioid, selective NaV1.8 pain-signal inhibitor, was approved by the U.S. Food and Drug Administration in January 2025 for moderate-to-severe acute pain. Whether perioperative suzetrigine use is associated with downstream outcomes after breast reconstruction remains unknown. OBJECTIVE To evaluate whether perioperative suzetrigine use after breast reconstruction is associated with differences in postoperative opioid use, emergency department visits, postoperative nausea/vomiting, hospital admission, antiemetic use, and naloxone administration, using a propensity score–matched retrospective cohort of a multicenter real-world electronic health record network. METHODS We conducted a retrospective cohort study using the TriNetX Global Collaborative Network (180 healthcare organizations). Women aged ≥18 years who underwent implant-based, expander-based, or autologous breast reconstruction were identified. Patients receiving suzetrigine within seven days of reconstruction comprised the exposed cohort; those without suzetrigine use within six months comprised the comparator cohort. Cohorts were balanced using 1:1 propensity score matching. Opioid use, emergency department visits, postoperative nausea/vomiting, hospital admission, antiemetic use, and naloxone administration were assessed 8–90 days postoperatively using risk and Kaplan-Meier analyses. RESULTS After matching, 334 patients were included in each cohort, with standardized mean differences <0.10 for nearly all covariates. Opioid use (36.5% vs. 32.3%), emergency department visits (3.9% vs. 5.1%), postoperative nausea/vomiting (3.6% vs. 4.8%), and naloxone use (4.5% vs. 6.3%) did not differ significantly. Hospital admission (9.9% vs. 5.4%, p =.029) and antiemetic use (37.7% vs. 25.7%, p=.001) were higher with suzetrigine. CONCLUSIONS Perioperative suzetrigine use was not associated with reduced opioid use or postoperative complications and was associated with higher hospital admission and antiemetic use. These findings may reflect confounding by indication or residual selection bias and should not be interpreted as causal. Prospective studies are needed to evaluate suzetrigine’s effectiveness and safety after breast reconstruction.