Why the study?
Opioid-related adverse events remain an important perioperative concern, prompting this review to analyze the pharmacokinetic, pharmacodynamic, and clinical evidence for suzetrigine.
Does suzetrigine provide effective and safe acute pain management compared to placebo or opioids in surgical patients?
Does suzetrigine provide effective and safe acute pain management compared to placebo or opioids in surgical patients?
Suzetrigine provides a unique, non-opioid mechanism to relieve acute pain with a favorable gastrointestinal side effect profile compared to traditional opioids.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“I actually see [suzetrigine] as something that can work in concert with some of our available nonopioid therapies, including nerve blocks.”
“Pain is a complex condition with multiple contributing factors, and no single medication will serve as a universal solution.”
“an important public health milestone in acute pain management…an opportunity to mitigate certain risks associated with using an opioid for pain and provides patients with another treatment option.”
Supports suzetrigine as a selective non-opioid option for postoperative pain with fewer GI effects; extends NaV1.8 inhibition evidence but leaves open broader multimodal trials.
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.
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Bach et al. (2026) conducted a review in Acute and perioperative pain. Suzetrigine vs. Placebo or hydrocodone/acetaminophen was evaluated.
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