Suzetrigine as Part of Multimodal Therapy Enables Opioid-Free Recovery after Laparoscopic or Arthroscopic Procedures.

INTRODUCTION: Suzetrigine, a non-opioid voltage-gated sodium channel 1.8 (NaV1.8) pain signal inhibitor with no addiction potential, is approved in the USA for moderate-to-severe acute pain. METHODS: In this phase 4, single-arm study, suzetrigine (100 mg preoperatively, then 50 mg every 12 h) was administered as part of multimodal therapy (MMT) for ≤ 14 days. Participants (N = 47) underwent arthroscopic or laparoscopic procedures wherein opioids are commonly used ≥ 72 h postoperatively for pain management. Pre- and postoperative MMT was prespecified as suzetrigine, acetaminophen, and ibuprofen. Oxycodone or hydromorphone were permitted as opioid rescue. The primary endpoint was the proportion of participants reporting good/very good/excellent on a patient global assessment (PGA) for pain control after treatment. Opioid rescue and safety were also assessed. RESULTS: Participants had various surgeries, the most common being arthroscopic knee procedures (38.3%) or rotator cuff repair (17.0%), and laparoscopic hernia repair with mesh (29.8%). Most participants (90.9%) rated suzetrigine as part of MMT as good/very good/excellent on a PGA for pain control at end of treatment; results were consistent across surgeries. A majority of participants (76.1%) did not require opioid rescue; those who did received 2.2 tablets (mean) after surgery (mean: 1.7 days). Suzetrigine was generally safe and well tolerated. One participant had a serious adverse event (aspiration) considered unrelated to suzetrigine. Adverse events were consistent with postoperative settings. CONCLUSIONS: Suzetrigine demonstrated effective pain management and enabled opioid-free recovery for most participants when initiated preoperatively and as part of MMT in arthroscopic or laparoscopic procedures wherein opioids are commonly used postoperatively for pain management. In studies of similar surgeries, < 50% did not require opioids. Graphical abstract available for this article. TRIAL REGISTRATION: NCT06887959.