Suzetrigine-Based Multimodal Therapy Enables Opioid-Free Recovery in Patients Receiving Surgery

Suzetrigine (Journavx; Vertex Pharmaceuticals), administered as part of a multimodal pain regimen, enabled more than 75% of patients undergoing laparoscopic or arthroscopic procedures to recover without postoperative opioid rescue medication, according to findings from a phase 4 study (NCT06887959) published in Pain and Therapy.¹

Among 47 patients treated with suzetrigine in combination with acetaminophen and ibuprofen, 76.1% did not require oxycodone or hydromorphone after surgery. Additionally, 90.9% of participants rated their pain control as good, very good, or excellent at the end of treatment.¹

The findings expand the postoperative evidence for suzetrigine beyond the controlled surgical models that supported its FDA approval, providing additional insight into how the first-in-class nonopioid analgesic may be incorporated into multimodal pain protocols for procedures in which opioids are commonly used for several days after surgery.^1,2

Evaluating Suzetrigine Across Common Surgical Procedures

The single-arm phase 4 clinical trial enrolled 47 adults undergoing laparoscopic or arthroscopic procedures in which postoperative opioid use commonly extends for at least 72 hours. The most frequently performed procedures included arthroscopic knee surgery (38.3%), laparoscopic repair with mesh (29.8%), and rotator cuff repair (17.0%).¹

Participants received a 100-mg loading dose of suzetrigine prior to surgery, followed by 50 mg every 12 hours for up to 14 days. The prespecified multimodal regimen also included acetaminophen and ibuprofen, with oxycodone or hydromorphone permitted as rescue therapy when additional analgesia was needed.¹

The primary end point was the proportion of patients who rated their overall pain control as good, very good, or excellent on a patient global assessment at the end of treatment. Investigators also assessed opioid rescue use and safety. Overall, approximately 90.9% of participants reported good, very good, or excellent pain control, with similar findings observed across the different surgical procedures included in the study.¹

Majority of Patients Avoided Postoperative Opioids

One of the major key findings was the limited use of opioid rescue medication. Approximately 76.1% of patients completed postoperative recovery without requiring oxycodone or hydromorphone. Among the minority who did require opioid rescue, patients used a mean of 2.2 tablets after surgery, with opioid use lasting an average of 1.7 days.¹

The investigators noted that previous studies evaluating comparable laparoscopic and arthroscopic procedures have generally reported opioid-free recovery in fewer than half of patients, highlighting the potential of a suzetrigine-based multimodal regimen to reduce postoperative opioid exposure.¹

These findings are particularly relevant as health care professionals continue to seek pain management strategies that provide adequate analgesia while minimizing unnecessary exposure to opioids following surgery. Although opioids remain an important option for patients with severe postoperative pain, reducing the amount and duration of opioid use may help limit opioid-related adverse effects and other risks associated with exposure. The FDA has similarly identified development of effective nonopioid analgesics as an important component of efforts to broaden acute pain treatment options.²

Building on Suzetrigine's Acute Pain Evidence

Suzetrigine is a first-in-class selective inhibitor of the voltage-gated sodium channel NaV1.8, which is expressed in peripheral pain-sensing neurons and contributes to transmission of nociceptive signals. Unlike opioids, which act within the central nervous system, suzetrigine acts on a peripheral pain-signaling pathway before pain signals reach the brain.^2,3

The FDA approved suzetrigine in January 2025 for the treatment of moderate to severe acute pain in adults, making it the first medication approved in a new class of nonopioid pain treatments. Clinical development initially focused heavily on standardized surgical pain models. Earlier randomized studies evaluated the drug following abdominoplasty and bunionectomy, providing evidence that selective NaV1.8 inhibition could reduce acute postoperative pain.^2,4

The new phase 4 findings broaden that evidence into laparoscopic and arthroscopic procedures and, importantly, evaluate suzetrigine as one component of multimodal therapy rather than as an isolated analgesic intervention. That distinction may be particularly relevant to clinical practice, where postoperative pain is often managed through combinations of agents with different mechanisms rather than a single medication.¹

Multimodal Pain Management May Offer a Practical Role for Suzetrigine

The results also provide insight into where suzetrigine may ultimately fit within postoperative treatment pathways. Rather than positioning the drug as a universal replacement for opioids, the phase 4 regimen incorporated suzetrigine alongside acetaminophen and ibuprofen while preserving opioids as rescue therapy when pain was not adequately controlled.¹

This approach allowed most patients to avoid opioid treatment entirely while ensuring that rescue analgesia remained available when needed. The strategy is consistent with the broader concept of multimodal analgesia, in which medications with different mechanisms are combined to improve pain control while potentially reducing reliance on any single drug class.

For pharmacists, the introduction of suzetrigine into these regimens also creates medication-management considerations. Suzetrigine is metabolized through CYP3A pathways, and concomitant medications must be reviewed for potentially significant interactions. Strong CYP3A inhibitors are contraindicated, and dosing considerations apply with some other CYP3A-modifying therapies.²

Findings Require Confirmation in Larger Comparative Studies

Despite the encouraging results, the study has important limitations. For instance, the trial included only 47 patients and did not contain a randomized comparator group, preventing investigators from determining how much of the observed opioid reduction was specifically attributable to suzetrigine rather than the overall multimodal regimen. The comparison with opioid-free recovery rates reported in previous surgical studies is also indirect and cannot substitute for a head-to-head randomized comparison. Additionally, the procedures represented several different surgical settings, creating clinical heterogeneity within a relatively small study population.¹

Still, the findings provide additional prospective evidence that suzetrigine can be incorporated into postoperative multimodal therapy while allowing a substantial proportion of patients to recover without opioid rescue.

As experience with the first-in-class NaV1.8 inhibitor continues to expand beyond the studies that supported its initial approval, larger comparative and real-world investigations will be important for determining whether the reductions in opioid use observed in these phase 4 cohorts translate across broader surgical populations.

REFERENCES

1. Habib AS, Solanki D, Hoff J, et al. Suzetrigine as part of multimodal therapy enables opioid-free recovery after laparoscopic or arthroscopic procedures. Pain Ther. Published online August 8, 2026. doi:10.1007/s40122-026-00865-4

2. FDA. FDA approves novel non-opioid treatment for moderate to severe acute pain. January 30, 2025. Accessed August 10, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-novel-non-opioid-treatment-moderate-severe-acute-pain

3. Osteen JD, Immani S, Tapley TL, et al. Pharmacology and mechanism of action of suzetrigine, a potent and selective NaV1.8 pain signal inhibitor for the treatment of moderate to severe pain. Pain Ther. 2025;14(2):655-674. doi: 10.1007/s40122-024-00697-0

4. Jones J, Correll DJ, Lechner SM, et al. Selective inhibition of NaV1.8 with VX-548 for acute pain. N Engl J Med. 2023;389(5):393-405. doi:10.1056/NEJMoa2209870