Suzetrigine for Acute Pain in the Emergency Department: A First-in-Class NaV1.8 Blocker

Suzetrigine is the first selective, orally bioavailable inhibitor of the peripheral voltage-gated sodium channel NaV1.8. In January 2025, it became the first nonopioid analgesic approved by the US Food and Drug Administration in more than 2 decades. We review preclinical data, regulatory filings, and all published phase 2 to 3 randomized, double-blind trials conducted to describe its potential role in emergency department (ED) pain management. The target receptor, NaV1.8, is critical for nociceptor firing yet absent from the central nervous system and cardiac tissue. This means suzetrigine provides analgesia without respiratory depression, euphoric effects, or arrhythmogenic risk. In 3 phase 3 studies of patients with acute pain, mostly from surgical causes, suzetrigine produced clinically meaningful reductions in 48-hour pain scores vs placebo and analgesia equivalent to hydrocodone/acetaminophen. Perceptible relief began at 60 minutes, peaking at 240 minutes as reported in these studies. Adverse events were reported as infrequent and mild, with no observed signals for abuse liability or respiratory compromise. Transient, asymptomatic declines in estimated glomerular filtration rate (≤2.5%) resolved spontaneously. Prospective ED studies are needed to confirm effectiveness, evaluate cost and formulary barriers, assess efficacy in nonsurgical pain, and determine the effects of long-term use. Studies of suzetrigine's use in the ED for nonsurgical pain must be conducted to ensure proper utilization. However, suzetrigine's oral formulation, preliminary favorable safety profile, and apparent lack of addictive potential based on early-stage trials align well with contemporary ED guidelines that prioritize multimodal, opioid-sparing analgesia, making it a promising addition to the armamentarium for pain management in the ED.