Suzetrigine as an Alternative to Opioids in Oncologic Pain Management

Background

Pain affects about 55% of patients during anticancer treatment and 66% of those with advanced or metastatic disease. Opioids remain the backbone of treatment, but constipation, sedation, delirium, respiratory depression, and misuse risk limit their use. Suzetrigine (JOURNAVX®) is a first-in-class, selective NaV1.8 sodium channel inhibitor. It was approved by the US FDA in January 2025 for moderate-to-severe acute pain in adults. NaV1.8 is expressed almost exclusively in peripheral nociceptors, so suzetrigine blocks pain signaling without the central effects of opioids. Its role in cancer patients has not been defined.

Objectives

To summarize the mechanistic rationale and the clinical evidence for suzetrigine, and to identify realistic uses, safety concerns, and research priorities in oncologic pain management.

Methods

In January 2025, the US FDA approved suzetrigine for moderate-to-severe acute pain in adults. The dose is 100 mg, then 50 mg every 12 hours, for up to 14 days. In two phase 3 trials after abdominoplasty and bunionectomy (more than 2,000 patients), suzetrigine was superior to placebo but not to hydrocodone/acetaminophen, and caused less nausea and vomiting. In a phase 2 trial in lumbosacral radiculopathy, suzetrigine did not separate from placebo. In cancer, the only clinical report is a case series of three opioid-tolerant men with spinal metastases. None had meaningful relief, and none had adverse effects. Its most plausible role in oncology is perioperative pain after cancer surgery, such as mastectomy, thoracotomy, or skin cancer excision, as part of a multimodal opioid-sparing regimen. A trial after skin cancer surgery is already registered. Short procedural pain, such as bone marrow biopsy or port placement, could be another use. Knocking down NaV1.8 reduced pain in a rat bone cancer model, but neuropathy after chemotherapy involves oxidative stress, neuroinflammation, and central sensitization, which a sodium channel blocker alone is unlikely to overcome. Several safety precautions matter in cancer patients. Suzetrigine is metabolized by CYP3A. It is contraindicated with strong CYP3A inhibitors, including the azole antifungals often used in hematologic malignancies. Strong or moderate inducers such as enzalutamide, apalutamide, carbamazepine, and rifampin can reduce its effect. It should be avoided in severe hepatic impairment and when eGFR is below 15 mL/min. The most common adverse effects are pruritus, muscle spasms, rash, and elevated creatine kinase.

Conclusions

Before suzetrigine can be recommended in oncology, randomized trials are needed. They should start with perioperative settings in cancer surgery and should measure pain scores, opioid consumption, and persistent postsurgical pain. Later studies should look at neuropathic cancer pain, stratified by pain phenotype, chemotherapy class, and opioid exposure. Long-term safety and interactions with anticancer drugs also need study. If these trials are positive, suzetrigine could reduce opioid exposure in cancer patients, particularly survivors and patients undergoing surgery. It would not replace opioids in advanced cancer pain, but it could add a non-sedating, non-addictive option to multimodal care that targets pain at its peripheral source.