Suzetrigine Was More Effective Than Placebo and Similar to Hydrocodone-Acetaminophen, 5 mg/325 mg for Postoperative Pain

Is suzetrigine (Journavx) safe and effective for postoperative pain?

Suzetrigine is a novel analgesic given every 12 hours that provides modest postoperative pain reduction similar to hydrocodone-acetaminophen, 5 mg/325 mg given every 6 hours. The dose and interval for the comparator are at the low end of the range. It would have been helpful for the study to include a nonopioid comparator such as ibuprofen, 600 mg, but it did not. Suzetrigine costs $15.50 per tablet ($227 for a 1-week course). (Level of Evidence = 1b)

Suzetrigine is a novel analgesic that inhibits the voltage-gated sodium channel 1.8, which transmits action potentials in peripheral nerves. Because it works peripherally, in theory, it should not be addictive. In the two industry-sponsored phase 3 trials, researchers identified adults 18 to 80 years of age who had undergone abdominoplasty with general anesthesia (n = 1,118) or unilateral bunionectomy with a field block or regional anesthesia (n = 1,073). Patients with moderate or severe postoperative pain (defined as at least a 4 on a 10-point visual analog scale) were randomized in a 2:2:1 ratio to receive a loading dose of suzetrigine, 100 mg, then 50 mg every 12 hours; hydrocodone-acetaminophen, 5 mg/325 mg every 6 hours; or placebo.

The double-blind, double-dummy design meant that all participants got the same number of pills at the same intervals. Pain on the 10-point scale was recorded 19 times during the 48-hour follow-up period, initially every 30 minutes, then every 60 minutes, then every 4 hours. The groups were similar at baseline with a mean age of 42 years (abdominoplasty) and 48 years (bunionectomy), and mean pain scores of 7.4 (abdominoplasty) and 6.8 (bunionectomy). The primary outcome was a complicated measure called SPID48, which is the sum of the differences from baseline to the recorded pain at the 19 measurements, each multiplied by the number of hours since the last measurement (range 0 to approximately 7 x 48 = 336). The SPID48 was significantly better for suzetrigine than placebo (118.4 vs 70.1; P < .0001 for abdominoplasty and 99.9 vs 70.6; P = .0002 for bunionectomy). There was no significant difference between suzetrigine and hydrocodone-acetaminophen. The time to a 2-point or greater reduction in pain from baseline was faster with suzetrigine than placebo (119 vs 480 minutes [P < .001] for abdominoplasty and 240 vs 480 minutes [P = .002] for bunionectomy). Adverse event rates were similar to placebo.

Study design: Randomized controlled trial (double-blinded)

Funding source: Industry

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

Editor’s Note: Dr. Ebell is deputy editor for evidence-based medicine for AFP.

Reference: Bertoch T, D’Aunno D, McCoun J, et al. Suzetrigine, a nonopioid Na V 1.8 inhibitor for treatment of moderate-to-severe acute pain: two phase 3 randomized clinical trials. Anesthesiology. 2025;142(6):1085-1099.