Suzetrigine brings another modality for pain management
A novel non-opioid analgesic FDA approved for acute pain
Suzetrigine (Journavx) is a non-opioid analgesic which selectively inhibits voltage-gated sodium channel 1.8 (NaV 1.8) blocking peripheral pain signals. Because NaV 1.8 is not present in the brain, suzetrigine is thought to be non-addictive. The recommended dosing is 100 mg taken on an empty stomach followed by 50 mg every 12 hours which can be taken with food. Its use beyond 14 days has not been studied. Could this pill help reduce the use of opioids while avoiding some of their worst side effects?
In two randomized controlled trials, suzetrigine was used to treat pain following either abdominoplasty or bunionectomy with participants being divided into three arms: suzetrigine, hydrocodone 5 mg + acetaminophen 325 mg, and placebo. All patients in the bunionectomy group had a continuous popliteal sciatic nerve block catheter with ropivacaine 0.2% which was discontinued on postop day one prior to randomization. All groups were allowed to have ibuprofen to treat breakthrough pain. No other NSAIDs or opioids were permitted.
The primary endpoint was the time-weighted sum of the pain-intensity difference over 48 hours (SPID48) following the first dose of the randomized drug. With this metric, a higher number shows greater pain relief, and a negative SPID would indicate worsening pain. The least squares mean difference compared to placebo was 48.3 (95% CI 33.6 to 63.1 p < 0.0001) following abdominoplasty and 29.3 (95% CI 14.0 to 44.6 p < 0.0002) following bunionectomy. There was no significant difference when comparing suzetrigine to the hydrocodone + acetaminophen groups.
Side effects were similar with suzetrigine and placebo. The most common side effects were nausea, vomiting, constipation, headache, dizziness, and hypotension. The incidence of nausea or vomiting was significantly lower with suzetrigine compared to hydrocodone (n = 91 vs n = 150 with abdominoplasty and n = 39 vs n = 71 with bunionectomy for suzetrigine and hydrocodone, respectively).
While the similar efficacy to hydrocodone makes suzetrigine seem like a promising new medication, some important caveats and unanswered questions remain. Rescue medication (ibuprofen) use was similar between suzetrigine and placebo. However, rescue medication use was not compared to the hydrocodone groups. If that group received significantly less ibuprofen than the suzetrigine groups, it could make suzetrigine appear more effective than it really is. This is the biggest point giving me pause. On the other hand, if everyone in the suzetrigine group had been given acetaminophen, would that group have had superior pain control compared to hydrocodone?
Other major limitations include a patient population in which most participants were female (98% in abdominoplasty and 85% in bunionectomy groups) and white (70 and 71% in the two trials). Patients taking chronic opioids or NSAIDs were excluded limiting the ability to generalize the results to a chronic pain population. Suzetrigine’s use as part of a multimodal approach was similarly not evaluated.
Fortunately, more clinical trials are ongoing. I hope we will see suzetrigine evaluated alongside regional anesthesia to ensure its safety when co-administered with local anesthetics which are non-specific voltage-gated sodium channel blockers. In the meantime, I would approach suzetrigine use with cautious optimism.