Na V 1.8 Inhibition and the Future of Nonopioid Analgesia in Otolaryngology

Importance: Postoperative pain management in otolaryngology requires balancing effective analgesia while minimizing adverse effects, such as opioid-related complications. Suzetrigine is a first-in-class selective voltage-gated sodium channel (NaV1.8) inhibitor that has been recently approved by the US Food and Drug Administration. Suzetrigine selectively inhibits NaV1.8 channels expressed in peripheral nociceptive neurons, thereby reducing pain signaling without the respiratory depression, sedation, or misuse potential associated with opioids. This review summarizes the pharmacology, efficacy, safety profile, limitations, and potential applications of suzetrigine in otolaryngology. Observations: Prospective clinical trials consist of 2 phase 2 randomized clinical trials, 2 phase 3 randomized placebo-controlled trials, and 1 phase 3 open-label study involving more than 3000 patients. Across abdominoplasty and bunionectomy pain models, suzetrigine demonstrated superior analgesia compared with placebo and mixed efficacy comparable to hydrocodone/acetaminophen. The drug was generally well tolerated, with adverse event rates similar to placebo and no significant respiratory, cardiac, or sedating adverse effects reported. Additionally, 1 retrospective cohort study has reported results in patients undergoing free flap reconstruction and transoral robotic surgery. Conclusions and Relevance: Suzetrigine is a promising nonopioid analgesic with demonstrated efficacy compared to placebo in acute postoperative pain and a favorable safety profile. In otolaryngology, suzetrigine may serve as an adjunct to multimodal analgesia and an opioid-sparing option for patients with contraindications to traditional analgesics, opioid use disorder, or procedures that are expected to have high opioid utilization such as tonsillectomy, sleep surgery, and major head and neck surgery. Future studies in otolaryngology are warranted to evaluate whether suzetrigine can meaningfully reduce postoperative opioid exposure without compromising analgesic effectiveness.