Suzetrigine, a Nonopioid Na V 1.8 Inhibitor for Treatment of Moderate-to-severe Acute Pain: Two Phase 3 Randomized Clinical Trials.

Summary

Across two large phase 3 RCTs in abdominoplasty and bunionectomy, suzetrigine significantly improved SPID48 vs placebo and provided analgesia similar to hydrocodone/acetaminophen, with a faster onset than placebo and mild-to-moderate adverse events. These results position a selective NaV1.8 inhibitor as a viable nonopioid option for acute postoperative pain.

Key Findings

• Met primary endpoint: SPID48 improved vs placebo in both trials (LS mean difference 48.4 after abdominoplasty; 29.3 after bunionectomy).
• No superiority over hydrocodone/acetaminophen on SPID48 in either trial.
• Faster onset to ≥2-point pain reduction vs placebo (119 vs 480 min abdominoplasty; 240 vs 480 min bunionectomy).
• Adverse events were mild to moderate and consistent with postsurgical settings.

Clinical Implications

Suzetrigine could be incorporated into multimodal analgesia pathways as an opioid-sparing agent for 48-hour postoperative pain control in soft-tissue and orthopedic procedures, with monitoring for class-specific adverse events.

Limitations

• Did not demonstrate superiority to hydrocodone/acetaminophen on SPID48
• Evidence limited to 48-hour postsurgical pain in two surgical models; long-term safety and broader generalizability remain to be established

Future Directions

Head-to-head comparisons with NSAIDs and regional techniques, evaluation across diverse surgeries and ambulatory settings, longer-term safety, and opioid-sparing outcomes (consumption, adverse events) in multimodal pathways.