Anesthesia Patient Safety Podcast

#265 The Breakthrough Drug Changing Perioperative Pain Management

• Anesthesia Patient Safety Foundation • Episode 265

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A revolution in pain management has arrived. The FDA's approval of Suzetrigine in January 2025 introduces the first non-opioid analgesic for moderate to severe pain in over twenty years. This breakthrough medication targets the voltage-gated sodium channel, NAV1.8, effectively blocking pain signals at their source before they reach the brain.

What makes Suzetrigine remarkable is its precision. With over 30,000-fold selectivity for NAV1.8 channels, it delivers powerful analgesia without affecting the brain or heart, eliminating addiction risk, and minimizing side effects. Clinical trials involving over 2,100 patients demonstrated pain relief comparable to opioid-acetaminophen combinations but with a safety profile similar to placebo. For the more than 50% of surgical patients who experience moderate to severe postoperative pain, this non-addictive alternative represents a genuine breakthrough. Looking ahead, an exciting pipeline of additional NAV1.8 channel blockers, including intravenous formulations, promises to further transform perioperative pain management.

Have you struggled with limited options for managing your patients' postoperative pain? Subscribe to the Anesthesia Patient Safety Podcast for more on groundbreaking developments like Suzetrigine that are changing how we approach patient care and safety. Leave us a review to share your thoughts on this revolutionary advance in pain management.

For show notes & transcript, visit our episode page at apsf.org: https://www.apsf.org/podcast/265-the-breakthrough-drug-changing-perioperative-pain-management/

© 2025, The Anesthesia Patient Safety Foundation

Speaker 1:

You're listening to the Anesthesia Patient Safety Podcast, the official podcast of the Anesthesia Patient Safety Foundation. We're bringing you the very best from the APSF newsletter and website, as well as the latest information in perioperative patient safety. Thanks for joining us.

Speaker 2:

Hello and welcome back to the Anesthesia Patient Safety Podcast. My name is Allie Bechtel and I'm your host. Thank you for joining us for another show. We are so excited to be talking about the excellent articles from the June 2025 APSF newsletter. Last week, we talked about considerations for specialized advanced cardiac life support training and protocols for when these critical events occur in the operating room. This week, we are opening the anesthesia drug drawer and talking about a new medication. So grab your headphones, because here we go. Here we go.

Speaker 2:

Before we dive into the episode today, we'd like to recognize Blink, a major corporate supporter of APSF. Blink has generously provided unrestricted support to further our vision that no one shall be harmed by anesthesia care. Thank you, Blink. We wouldn't be able to do all that we do without you. Our featured article today is Suzette Trujillo, a novel peripherally acting analgesic by Paul Lee, Michael Kim, Joseph Skokal and Michael Batros. To follow along with us, head over to APSForg and click on the newsletter heading. The first one down is the current newsletter. Then scroll down until you get to our featured article today, and I will include a link in the show notes as well. We have exclusive content from one of the authors to help us kick off the show, let's take a listen now.

Speaker 3:

My name is Joseph Sulklin. I'm a professor of clinical anesthesia in the Department of Anesthesiology and Paraph Medicine at UCLA Health in Los Angeles, california. Most recently, I was a professor of clinical anesthesiology at the Keck School of Medicine at USC, where I served as the executive director of mentorship and physician development, as well as the Co-Director of Quality and Patient Safety. We chose to write this article for the importance of appropriate pain control in the para-epidemic period.

Speaker 3:

On January 30, 2025, the US Food and Drug Administration approved the drug suzetrogene, a first-in-class non-open analgesic to treat moderate to severe pain in adult patients having surgery. Suzetrogene is a novel small molecule that binds tightly to the NAV1.8 channel, with 31,000 to 1 selectivity over other NAV channels. Despite approval of numerous analgesic agents throughout the 20th century, greater than half of surgical patients still experience moderate to severe post-operative pain. Suzetrogen, a non-opiate, non-addictive, selective 1.8 pain signal inhibitor, holds the potential to be the first treatment for moderate to severe pain in a new pharmacal class in over two decades. Suzetrogen is the first non-opiate analgesic to receive FDA approval since 2004, when the FDA approved pregabalin. We know that poorly treated pain can lead to chronic pain, so it is vital to treat pain preemptively.

Speaker 2:

Thank you so much to Skokul for helping to introduce this exciting article and, more importantly, this new medication. And now it's time to get into the article. Do you remember what you were doing on January 30th 2025? That is the day that the US Food and Drug Administration approved the drug Jornovix or Suzetrogene to treat moderate to severe pain in adult patients. This is a first-in-class non-opioid analgesic medication. We are not the only ones excited about this new medication. Jacqueline Corrigan-Curry, the acting director of the FDA's Center for Drug Evaluation and Research, states that this is an important public health milestone in acute pain management by providing a non-opioid treatment option for pain management. This article highlights two of the APSF's patient safety priorities medication safety and opioid-related harm. We need to learn all about this new medication.

Speaker 2:

Suzetrogene is the first drug to be approved in a new class of pain management medications. That's right. It is not an opioid medication and it will likely have a big impact on perioperative pain management and help to mitigate opioid-related harm going forward. Did you know that over half of surgical patients still experience moderate to severe postoperative pain? We have work to do in this area. Let's meet the newcomer in the medication drawer.

Speaker 2:

Suzetradine is a non-opioid, non-addictive, selective pain signal inhibitor. This may be the first treatment for moderate to severe acute pain in a new pharmacologic class in over 20 years. The mechanism of action is inhibition of the voltage-gated sodium channel NAV1.8, channel NAV1.8, by binding to the protein's second voltage sensing domain, vsd2, to stabilize the closed state of the channel. This novel allosteric mechanism leads to tonic inhibition of NAV1.8 and reduces pain signals in the primary human dorsal root ganglion sensory neuron pain signals. In the primary human dorsal root ganglion sensory neuron. The pain signals are blocked in the nociceptive C fibers before they are allowed to reach the brain. This opioid alternative is safe without the risk of addiction or organ toxicity.

Speaker 2:

Researchers have learned that acute neuropathic pain or inflammatory pain is caused by excessive firing of dorsal root ganglion or DRG neurons or trigeminal ganglion neurons. In addition, different sodium channel genes have been identified. Then the search was on for a peripheral sodium channel that was involved in DRG neuron firing but not in the brain or in the heart. It was a sodium channel scavenger hunt and three such channels were identified NAV 1.7, nav 1.8, and NAV 1.9 that regulate peripheral pain signaling in nociceptive C fibers. Nav 1.8 was found to be responsible for more than 70% of the current allowing propagation of the action potential. As the main contributor, this channel became the primary target. Check out figure 1 in the article to see the voltage-gated sodium channels that are involved in generation and propagation of pain signals. There are 9 of these channels that are named NAV1.1 through NAV1.9, and each channel has a unique cell-type-specific expression pattern and function. Non-selective voltage-gated sodium channel blockers can affect multiple systems, but NAV1.7, nav1.8, and NAV1.9 are highly expressed in peripheral sensory neurons and are essential for initiation and propagation of pain signals in peripheral nociceptive neurons.

Speaker 2:

Let's focus on our new medication, suzectrogene, which inhibits depolarization in peripheral pain signaling neurons without an effect on the brain or the heart. This is great news, since it means that there is a reduction in pain with few central nervous system or cardiac side effects. In vitro studies have revealed a greater than 30,000-fold selectivity for NAV1.8 channels for suzetrogene, unlike non-selective sodium channel blockers. Non-selective sodium channel blockers. Figure 2 in the article highlights future NAV1.8 molecules that are being studied and evaluated in different phases, from the research phase all the way to phase 3 trials with different formulations, including oral and intravenous, and for the treatment of acute pain and peripheral neuropathic pain. I will include both figures 1 and 2 in the show notes as well.

Speaker 2:

Vertex Pharmaceuticals tested the safety and efficacy of suzetrogene with two large randomized clinical trials that included over 1,100 patients undergoing abdominoplasty and over 1,000 patients undergoing bunionectomy. There were three groups of patients a placebo, a combination of acetaminophen and hydrocodone, or suzetrogene. Suzetrogene is administered with 100 mg oral loading dose, followed by 50 mg every 12 hours. Patients received the randomized treatment and anyone who experienced breakthrough pain were permitted to use ibuprofen for rescue analgesia. The results from both trials revealed statistically significant superior reduction in pain with Suzetrogene compared to placebo. Superiority compared to hydrocodone and acetaminophen was not demonstrated, but a responder's analyses at 12 hours, 24 hours and 48 hours showed similar reductions in numeric pain rating scale of 30%, 50% and 70% respectively with suzetrogene when compared to hydrocodone and acetaminophen. Suzetrogene side effects were similar to placebo.

Speaker 2:

Additional considerations include an increased risk of adverse reactions with the concomitant use of moderate to strong CYP3A inhibitors. Risk for drug interactions with certain hormonal contraceptives. Thus, patients taking suzetrogene should use non-hormonal contraceptives or use alternative contraceptives containing levonorgestrel and norethindrone. Patients with moderate to severe hepatic impairment may have higher systemic levels of suzetrogene and its active metabolites. This medication should be avoided for patients with severe renal impairment and a GFR less than 15 mLs per minute, and patients should avoid food and drink containing grapefruit when taking suzetrogene. The most common adverse effects were itching, muscle spasms, increased blood levels of creatine, phosphokinase and rash. The good news is that suzetrogene is safe and well-tolerated, with a lower incidence of adverse events compared to placebo and acetaminophen-hydrocodone combination.

Speaker 2:

Have you ever evaluated a patient with moderate to severe postoperative pain and thought I wish there was another non-opioid option available for treatment? Well, suzetrogene might be the answer we have been looking for to help with improved pain management and recovery. Let's run through the facts about this new medication one more time. It is a safe, effective and non-addictive medication that can provide a new option for patients at high risk for opioid-related adverse events or when non-steroidal anti-inflammatory drugs are contraindicated. It may be an important component for future ERAS protocols.

Speaker 2:

Fda approval occurred on January 30, 2025 for the oral treatment of moderate to severe pain. It works as a selective sodium channel blocker that works at the voltage-gated sodium channel NAV1.8, which can be found in the peripheral dorsal root ganglion neurons. Notably, it is the first sodium channel to be approved in the US for this indication and it is the first non-opioid drug to be approved for the treatment of pain in more than 25 years. Suzetrodine has no abuse potential and no known organ toxicity. This is a very exciting development for perioperative pain management and the treatment of acute pain. Before we wrap up for today, I also asked Skokul what he envisions for the future when it comes to this novel medication. This is what he had to say.

Speaker 3:

Post-operative pain control is a vital component to proper recovery for surgical patients. One major component of successful programs, such as the enhanced recovery after surgery ERAS protocols, is optimizing pain control through the entire period. This starts with preoperative loading of acetaminophen and NSAIDs, and now suzetrogene, which acts synergistically with other analgesics. Intraoperatively, postoperative pain is additionally minimized with regional anesthetics, which includes single-shot blocks and catheters. There is a large pipeline of future NAV.8 molecules, both oral and IV, by Vertex and other pharma companies, which hopefully lead to additional non-addictive, safe and effective treatment for post-operative pain.

Speaker 2:

Thank you so much to Skokul for contributing to the show today and helping to highlight this exciting new medication. We are looking forward to learning more about suzetrogene and using this medication option to help improve pain control during the perioperative period. We will also need to watch this space for the development of new medications in this class, especially once an IV formulation is available. If you have any questions or comments from today's show, please email us at podcast at APSForg. Please keep in mind that the information in this show is provided for informational purposes only and does not constitute medical or legal advice. We hope that you will visit APSForg for detailed information and check out the show notes for links to all the topics we discussed today.

Speaker 2:

The APSF is delighted to announce the inaugural digital editor program. This is a paid one-year program for an anesthesia professional or anesthesia professional in training with a talent for medical communications and digital media. Grow your skills in medical journalism and launch your career with networking and mentorship from the APSF. The deadline is August 1st. Check out the link in the show notes or head over to apsforg for more information. Until next time, stay vigilant so that no one shall be harmed by anesthesia care.