Phase 4 Study: 91% of Patients Avoid Opioid Rescue With Suzetrigine-Based Multimodal Therapy After Plastic Surgery

A suzetrigine (Journavx; Vertex Pharmaceuticals)-based multimodal pain regimen was associated with opioid-free recovery for approximately 91% of patients following aesthetic or reconstructive surgery, according to findings from a phase 4 study (NCT06887972) published in Plastic and Reconstructive Surgery.¹ The results extend the evidence for suzetrigine beyond the controlled postoperative settings evaluated in its pivotal trials and offer an early look at how the first-in-class nonopioid analgesic may be incorporated into procedure-specific multimodal pain protocols.¹˒²

Among 99 adults treated with suzetrigine before surgery and for up to 14 days afterward, 90.9% did not require postoperative opioid rescue medication. Additionally, 90.7% rated their pain control as good, very good, or excellent at the end of treatment.¹ Although the single-arm study cannot establish that suzetrigine caused these outcomes or that the regimen was superior to conventional care, the findings suggest a potential strategy for reducing opioid exposure after procedures for which opioids are commonly prescribed.¹

Evaluating Preoperative Suzetrigine in Multimodal Therapy

Suzetrigine is a highly selective inhibitor of the voltage-gated sodium channel NaV1.8, which is expressed in peripheral pain-sensing neurons. By inhibiting pain signaling in the peripheral nervous system before it reaches the brain, the agent provides analgesia through a mechanism that does not directly activate opioid receptors. The FDA approved suzetrigine in January 2025 for the treatment of moderate-to-severe acute pain, including postoperative pain, in adults.²˒³

The phase 4 single-arm study evaluating the effectiveness and safety of suzetrigine for acute pain enrolled 99 adults undergoing aesthetic or reconstructive procedures for which opioids would commonly be used for at least 72 hours after surgery. The most frequently represented procedures were aesthetic breast surgery (33.3%), abdominoplasty with liposuction (28.3%), reconstructive breast surgery (13.1%), and turbinoplasty (13.1%).¹

Patients received 100 mg of suzetrigine before surgery, followed by 50 mg every 12 hours as part of a multimodal regimen for up to 14 days or until their pain resolved. Investigators selected the accompanying therapies, with acetaminophen and/or ibuprofen recommended.¹

Most patients (78.8%) received suzetrigine with acetaminophen, ibuprofen, or both, whereas 12.1% received suzetrigine without either medication. These variations indicate that suzetrigine was evaluated as part of individualized multimodal treatment rather than a single standardized combination regimen.¹

The primary end point was the proportion of patients who rated their pain control as good, very good, or excellent on a patient global assessment at the end of treatment. Investigators also evaluated opioid rescue medication use, safety, and tolerability.¹

Most Patients Avoided Postoperative Opioids

At the end of treatment, 90.7% of patients rated the effectiveness of their pain regimen as good, very good, or excellent. Favorable assessments were generally consistent across the different categories of surgery.¹

Most notably, 90.9% of patients required no opioid rescue medication after surgery. Among the 9 patients who required opioid rescue, mean use was 2.4 tablets over an average of 2 days.¹ These findings suggest that even when opioid rescue remained necessary, the amount and duration of exposure were limited within this study population.

The investigators contrasted the findings with previously published reports of mixed cosmetic procedures in which fewer than 10% of patients avoided opioids.¹ However, that comparison was based on historical literature rather than a concurrent control group. Differences in surgical techniques, prescribing practices, patient selection, background analgesia, and outcome measurement prevent a direct conclusion that the suzetrigine regimen produced superior opioid avoidance.¹

The findings nevertheless address an important question left open by suzetrigine’s pivotal phase 3 program. In 2 randomized trials involving 2191 adults with moderate-to-severe acute pain after abdominoplasty or bunionectomy, suzetrigine produced statistically significant pain reduction compared with placebo. Pain reduction was similar to that observed with hydrocodone bitartrate/acetaminophen, although neither trial met the secondary end point of suzetrigine superiority over the opioid-containing comparator.⁴

Unlike those trials, the phase 4 study evaluated suzetrigine when initiated preoperatively and incorporated into a multimodal regimen that could continue during recovery.¹˒⁴ That distinction makes the study particularly relevant to pharmacists and health systems developing perioperative pathways intended to minimize—but not necessarily eliminate the availability of—opioid rescue therapy.

Safety Findings Remained Consistent With the Surgical Setting

Suzetrigine was generally well tolerated, and reported adverse events were described as consistent with the postoperative setting.¹ Because detailed information regarding specific serious adverse events was not provided in the published abstract, those events should not be characterized further without access to the complete peer-reviewed report.

According to the current prescribing information, the most common adverse reactions reported more frequently with suzetrigine than placebo were pruritus, muscle spasms, increased creatine phosphokinase, and rash. Concomitant use with strong CYP3A inhibitors is contraindicated, whereas dosage reduction is required with moderate CYP3A inhibitors. Use with strong or moderate CYP3A inducers should be avoided, as should grapefruit-containing food and beverages during treatment.³

The FDA-approved regimen begins with 100 mg taken on an empty stomach at least 1 hour before or 2 hours after food. Beginning 12 hours after the initial dose, patients receive 50 mg every 12 hours, with or without food. Treatment should be continued for the shortest duration consistent with individual treatment goals, and use beyond 14 days has not been studied.³

Pharmacists should also account for additional prescribing considerations, including dosage reduction in moderate hepatic impairment and avoidance in severe hepatic impairment. Suzetrigine may also interact with certain sensitive CYP3A substrates and hormonal contraceptives, making comprehensive medication reconciliation and patient counseling important components of its use.³

Pharmacists Can Help Translate Opioid Avoidance Into Practice

The phase 4 findings support further evaluation of suzetrigine within procedure-specific multimodal pain pathways.¹ Pharmacists can help determine where the medication fits relative to acetaminophen, nonsteroidal anti-inflammatory drugs, local anesthetic techniques, and opioid rescue therapy while accounting for patient-specific contraindications, hepatic function, and drug interactions.³

Implementation will require more than adding suzetrigine to a formulary. Pharmacists may contribute to preoperative medication review, development of order sets, CYP3A interaction screening, discharge coordination, outpatient access verification, and counseling regarding administration requirements. Health systems evaluating suzetrigine-based pathways should also measure pain control, rescue opioid requirements, functional recovery, adverse events, treatment cost, and unplanned care after discharge.

The findings should be interpreted in light of the study’s single-arm design, small population, reliance on a patient global assessment for the primary end point, and absence of a randomized concurrent comparator.¹ The study also included several authors affiliated with Vertex Pharmaceuticals.¹ Consequently, randomized pragmatic studies are needed to determine whether suzetrigine-based protocols reduce opioid use compared with contemporary multimodal care across broader surgical populations.

Even with these limitations, the results provide encouraging postapproval evidence that suzetrigine can be initiated before surgery as part of a multimodal strategy.¹ For pharmacists, the central question is shifting from whether a nonopioid NaV1.8 inhibitor can relieve acute pain to how it can be incorporated into routine care while preserving pain control and limiting unnecessary opioid exposure.

References

1. Lin SJ, McCoun J, Solanki D, et al. Suzetrigine as Part of Multimodal Therapy Enables Opioid-Free Recovery After Aesthetic or Reconstructive Procedures. Plast Reconstr Surg. Published online July 6, 2026. doi:10.1097/PRS.0000000000013299

2. FDA approves novel non-opioid treatment for moderate to severe acute pain. FDA. Published January 30, 2025. Accessed August 5, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-novel-non-opioid-treatment-moderate-severe-acute-pain

3. Journavx (suzetrigine) tablets, for oral use. Prescribing information. Vertex Pharmaceuticals Incorporated. Revised January 2026. Accessed August 5, 2026. https://pi.vrtx.com/files/uspi_suzetrigine.pdf

4. 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. doi:10.1097/ALN.0000000000005460