Suzetrigine: A Selective Inhibitor of the NaV1.8 Sodium Channel

Opioid related adverse events are an important perioperative concern despite widespread adoption of combined analgesic approaches for pain management. Suzetrigine, a selective inhibitor of the NaV1.8 sodium channel for the treatment of moderate-to-severe acute pain, enables the use of a novel analgesic class in clinical practice. The goal of this scoping review is to analyze suzetrigine's pharmacokinetic, pharmacodynamic, and clinical evidence. Utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines, the online databases of PubMed, Embase, and ClinicalTrials.gov (January 2020 to February 2026) were systematically searched for various studies investigating NaV1.8-selective compounds in acute pain contexts. A total of five reviewers screened and extracted data with cross-examination. A total of 10 articles were identified to meet the specified inclusion criteria for this scoping review. These articles were recognized as peer-reviewed publications, clinical trial registry results, regulatory documents, conference abstracts, and preprints. Suzetrigine was found to be most effective when given orally twice daily, and its selectivity for NaV1.8 was up to 30,000 times greater than that of other sodium channel medications pursuing the same effect. Suzetrigine was associated with a decrease in gastrointestinal symptoms when compared to opioid counterparts, a decrease of up to 40%. Mechanistic studies reveal that NaV1.8 inhibition reduces, but does not abolish, pain receptor firing, explaining the meaningful yet incomplete analgesia observed clinically. Suzetrigine is also metabolized by cytochrome P4503A (CYP3A) enzymes, suggesting potential drug interactions. Suzetrigine provides a unique mechanism to relieve acute pain without opioids. Current evidence gaps include limited data across comprehensive surgical populations, multimodal comparative effectiveness of trials, and undefined safety outcomes. Perioperative analgesic regimens can be optimized by prioritizing research addressing areas with insufficient evidence.