Suzetrigine for Postoperative Pain After Total Ankle Replacement

Total ankle arthroplasty (TAA) causes substantial acute postoperative pain, typically managed with multimodal analgesia including acetaminophen, NSAIDs, and as-needed opioids. Reducing early postoperative opioid exposure is a recognized priority.

Suzetrigine is a selective NaV1.8 sodium channel inhibitor acting on peripheral pain-sensing neurons. This single-arm, open-label prospective cohort study enrolls patients undergoing primary TAA who will receive suzetrigine in addition to standard multimodal analgesia. Outcomes are compared with a historical control group of patients who underwent primary TAA at the same institution during the preceding five years and received standard multimodal analgesia alone, identified retrospectively.

Inclusion criteria

• Adult patients aged 18-75 years Undergoing primary total ankle arthroplasty (TAA) Capable of completing questionnaires Capable of providing consent for enrollment Capable of using Suzetrigine times a day Capable of completing the follow-up visits

Exclusion criteria

• BMI ≥ 50 kg/m² Pre-operative/current opioid consumption Prior history of ipsilateral ankle infection Severe hepatic impairment (Child-Pugh Class C) eGFR < 30 ml/min Pregnant or lactating Heart failure or recent myocardial infarction Using strong CYP3A inhibitors (e.g., itraconazole) or strong/moderate CYP3A inducers (e.g., Rifampin) Women taking concomitant progestin-containing contraceptives other than levonorgestrel and norethindrone who are unwilling to use additional non-hormonal contraceptives (such as condoms) or alternative contraceptives during Suzetrigine treatment and for 28 days after discontinuation