FDA approves Journavx (Suzetrigine) as the first non-opioid treatment for moderate to severe acute pain

Dear Editor,

Acute pain is a sudden-onset condition that typically lasts less than 6 months and can significantly affect daily life, well-being, and healthcare costs. Management options include nonsteroidal anti-inflammatory drugs such as aspirin and ibuprofen, acetaminophen, corticosteroids, and opioids. In severe cases, opioids may be necessary, but their use is limited by side effects, such as hypoventilation, nausea, vomiting, constipation, CNS depression, and renal dysfunction[1]. Opioids continue to play a key role in pain management, but their use must minimize risks while maximizing benefits.

Opioids, which act on central mechanisms related to pain perception, are frequently used to manage acute pain. However, due to safety concerns, their use is restricted, and there is a high risk of dependence, addiction, and adverse effects[2]. These side effects have led to approaches aimed at reducing acute pain, though not without limitations. Rising misuse of prescription opioids has contributed to increased morbidity and mortality[3]. Non-opioid analgesics, which lack the risk of addiction, offer a promising alternative for moderate to severe acute pain. On 30 January 2025, the FDA approved Journavx (Suzetrigine) as the first non-opioid analgesic for moderate to severe acute pain, representing a major step forward in pain management[4].

As NaV1.8 is a tetrodotoxin-resistant voltage-gated channel, Suzetrigine has a pivotal role in pain perception. It binds to VSD2, the voltage-sensing domain, to inhibit NaV1.8 by a phenomenon called “reverse use dependence,” by which repetitive depolarizations decrease the inhibition of the channel. It has a major effect in decreasing the pain signals, especially in the dorsal root ganglion[5]. Two randomized double-blind controlled trials involving 303 patients and 274 patients for abdominoplasty and bunionectomy showcase the efficacy of this drug. Participants received Suzetrigine, hydrocodone tartrate-acetaminophen or placebo in variable doses. Results of the trial showed that participants who received high and middle doses experienced a significant reduction in pain compared to the other groups. However, lower doses did not show a significant difference from the placebo[2]. In contrast to the other opioids available, Suzetrigine has the least chances for drug dependence owing to the decreased SCN10A expression in the brain. It was also not associated with any respiratory depression or sedation, as was not the case in the hydrocodone tartrate-acetaminophen group. Treatment of pain is concerned with avoiding sufficient pain and providing maximum relief, along with preventing dependence. All these effects are expressed in the novel drug Suzetrigine, which has proven to be effective in post-operative care in contrast to its opioid counterparts[2]. This trial has certain limitations that need to be addressed. It focuses primarily on the female population; however, both abdominoplasty and bunionectomy, along with pain, are also present in males. This leads to insensitivity to sample size, predisposing to sample bias. Moreover, it also discusses the role of Suzetrigine as a monotherapy in these procedures. However, multiple therapeutic approaches are used for pain control. The trial also couldn’t compare the magnitude of pain relief due to Suzetrigine as compared to the hydrocode tartrate-acetaminophen group. All these factors need to be addressed properly in the future for effective Suzetrigine implementation as a monotherapy.

Suzetrigine represents a promising non-opioid analgesic acting on the NaV1.8 receptors, providing a novel approach for pain management through selective inhibition of the peripheral pain pathway. Clinical trials have shown that they have been effective in reducing moderate to severe acute pain with a favourable tolerability profile and minimal CNS involvement, significantly lowering the risk of addiction in comparison to opioids[5].

Common adverse effects experienced by individuals were nausea, constipation, headache, and dizziness[2]. Safety evaluations revealed no side effects on the cardiovascular system, central nervous system, and behaviour. In addition to this, no signs of addiction or dependence were found, likely due to the peripheral mode of action[5]. There are still many limitations, such as the safety of long-term use, as a trial in patients with diabetic neuropathy presented with decreased creatinine clearance after 12 weeks of high dosage[6].

Further ongoing trials aim to assess the efficacy of these agents in chronic pain conditions, including painful diabetic peripheral neuropathy and lumbosacral radiculopathy^[7,8]. Moreover, data regarding the safety and efficacy of this drug as part of multimodal analgesia, along with its use in pregnant women, are still required to determine if the potential risks of major birth defects or miscarriages are present. The safety and efficacy of this drug in the paediatric population also remain unexplored.

Further clinical trials are required to compare Suzetrigine’s efficacy and safety against opioids. Prospective studies should be focused on long-term safety profiles, the role of these drugs in multimodal analgesia, and efficacy in various patient categories. Despite these challenges, Journavx (Suzetrigine) presents a promising opioid alternative with a favourable safety profile. It could mean less opioid dependence and may have the potential to eliminate the risk of addiction and overdose in the management of pain. With its recent approval, there is an urgent need to conduct retrospective analyses and real-world studies to assess its relative effectiveness, long-term safety profile, and overall impact on diverse populations and clinical settings.

This manuscript was developed in accordance with the TITAN 2025 Guidelines for ethical and transparent use of AI in scholarly publishing (TITAN, 2025)[9].

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Ethics approval was not required for this editorial.

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This research received no specific funding.

Author contributions

M.B.A.: conceptualisation, writing – original draft, writing – review and editing. P.K.: writing – original draft, writing – review and editing. M.T.A.: writing – original draft. M.O.O.: supervision.

Conflicts of interest disclosure

The authors declared no conflicts of interest.

Guarantor

Muhammad Bilal Aamir.

Research registration unique identifying number (UIN)

Not applicable.

Provenance and peer review

Not commissioned, externally peer reviewed.

Data availability statement

Data sharing is not applicable to this article as no new data were created or analysed.