Suzetrigine

Suzetrigine is a new first-in-class, orally-available NaV1.8-selective sodium channel blocker for non-opioid treatment of moderate-to-severe acute pain. NaV1.8 channel inhibition, which is expressed almost exclusively in peripheral nociceptors, suppresses pain signal generation without central nervous system, cardiac or motor side effects, sedation, respiratory depression, or addiction. Suzetrigine is a highly potent and orally bioavailable NaV1.8 inhibitor with over 30,000-fold selectivity. The recommended dosage is 100 mg load dose, followed by 50 mg every 12 hours, supported by a 30–60 hour half-life. Suzetrigine rapidly alleviated pain with analgesic onset within 2 hours, and displayed pain relief significantly greater than placebo and similar to low-dose hydrocodone/acetaminophen. In addition, it had fewer GI/CNS adverse events and a lower discontinuation rate of <2%.
In the preclinical models, there were no signs of dependence or cardiotoxicity. Cost-effectiveness analyses are also promising and show potential to decrease total healthcare costs, and reduce the risk of opioid-use disorder relative to opioid therapies. Suzetrigine presents a safe, effective, and peripherally restricted alternative for the treatment of acute pain, with potential for a positive impact in the fight against the opioid crisis.

Fig. 1 Suzetrigine's mechanism of action. (Maciej M.; et al. 2025)