{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T01:52:43Z","timestamp":1792201963966,"version":"4.4.0"},"reference-count":29,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The discovery and approval of Suzetrigine (VX\u2010548, Journavx) marks a significant breakthrough in pain management. It is the first non\u2010opioid analgesic approved since celecoxib in 1998. Suzetrigine selectively blocks voltage\u2010gated sodium channel Na\n                    <jats:sub>v<\/jats:sub>\n                    1.8 and acts exclusively on peripheral nociceptors without crossing the blood\u2013brain barrier, providing analgesia while sparing central nervous system side effects such as dependence, addiction, sedation, and respiratory depression. In\u00a0vitro experiments have demonstrated that Suzetrigine is a state\u2010dependent inhibitor with nanomolar potency against human Na\n                    <jats:sub>v<\/jats:sub>\n                    1.8, exhibiting &gt;\u200931,000\u2010fold selectivity compared to other subtypes of sodium channels and molecular targets. Suzetrigine is rapidly absorbed following oral administration with peak plasma concentrations (\n                    <jats:italic>T<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    ) in approximately 3\u2009h under fasting conditions and an effective half\u2010life (\n                    <jats:italic>t<\/jats:italic>\n                    <jats:sub>1\/2<\/jats:sub>\n                    ) of 23.6\u2009h. Suzetrigine is primarily eliminated via hepatic metabolism. Recent phase II and III clinical trials have validated Suzetrigine's efficacy in acute postoperative pain settings, demonstrating statistically significant reductions in pain intensity over 48\u2009h following abdominoplasty and bunionectomy. Additionally, Suzetrigine has shown favorable safety and tolerability in broader acute pain indications and is under continued investigation for the treatment of chronic neuropathic conditions such as diabetic peripheral neuropathy. Pharmacokinetic and pharmacodynamic data support Suzetrigine's rapid oral absorption, state\u2010dependent Na\n                    <jats:sub>v<\/jats:sub>\n                    1.8 inhibition, and limited off\u2010target activity as confirmed by both nonclinical and clinical safety studies. Suzetrigine received approval for use in January 2025 in the United States only. Ongoing trials are exploring novel formulations, long\u2010term safety, and integration into multimodal regimens for surgical and non\u2010surgical pain.\n                  <\/jats:p>","DOI":"10.1111\/cts.70414","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T13:04:01Z","timestamp":1763471041000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Suzetrigine, a Non\u2010Opioid Small\u2010Molecule Analgesic: Mechanism of Action, Clinical, and Translational Science"],"prefix":"10.1111","volume":"18","author":[{"given":"Rhea","family":"Rajasingham","sequence":"first","affiliation":[{"name":"Nasuti College of Osteopathic Medicine Duquesne University  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7535-3340","authenticated-orcid":false,"given":"Yanfei","family":"Qi","sequence":"additional","affiliation":[{"name":"Nasuti College of Osteopathic Medicine Duquesne University  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"Institute for Clinical and Economic Review (ICER) Acute Pain: Final Evidence Report and Report\u2010At\u2010A\u2010Glance https:\/\/icer.org\/wp\u2010content\/uploads\/2025\/03\/Acute\u2010Pain_RAAG_March\u20102025.pdf."},{"key":"e_1_2_11_3_1","unstructured":"U.S. Food and Drug Administration FDA Approves Novel Non\u2010Opioid Treatment for Moderate to Severe Acute Pain Press Announcement https:\/\/www.fda.gov\/news\u2010events\/press\u2010announcements\/fda\u2010approves\u2010novel\u2010non\u2010opioid\u2010treatment\u2010moderate\u2010severe\u2010acute\u2010pain."},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000252951.48745.a1"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1398409"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/1744806919858801"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2209870"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.2147\/JPR.S509144"},{"key":"e_1_2_11_9_1","volume-title":"Vertex Announces Results From Phase 2 Study of Suzetrigine for the Treatment of Painful Lumbosacral Radiculopathy","author":"Vertex Pharmaceuticals [Internet]","year":"2024"},{"key":"e_1_2_11_10_1","unstructured":"ClinicalTrials.gov A Study to Evaluate the Relative Bioavailability and Food Effect of a New Tablet Formulation and Strength of Suzetrigine ClinicalTrials.gov Identifier: NCT06336096 accessed June 12 2025 https:\/\/clinicaltrials.gov\/study\/NCT06336096."},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1124\/molpharm.124.000944"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5490-08.2009"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13215"},{"issue":"8","key":"e_1_2_11_14_1","first-page":"2122","article-title":"A Phase 1, Randomized, Double\u2010Blind, Placebo\u2010Controlled Trial to Evaluate the Safety, Tolerability, Analgesic Efficacy, and Pharmacokinetics of VX\u2010150, a Pro\u2010Drug of a Highly Selective Nav1.8 Inhibitor, in Healthy Subjects","volume":"162","author":"Hijma H. J.","year":"2021","journal-title":"Pain"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40122-024-00697-0"},{"key":"e_1_2_11_16_1","unstructured":"ClinicalTrials.gov Pharmacodynamic Study of 100 mg Suzegtrigine vs Placebo in Healthy Male Adults ClinicalTrials.govIdentifier: NCT06972212 accessed July 10 2025 https:\/\/clinicaltrials.gov\/study\/NCT06972212."},{"key":"e_1_2_11_17_1","unstructured":"ClinicalTrials.gov Evaluation of the Effect of Suzetrigine (SUZ) on the Pharmacokinetics of Oral Contraceptives in Healthy Female Participants ClinicalTrials.govIdentifier: NCT06820307 accessed July 10 2025 https:\/\/clinicaltrials.gov\/study\/NCT06820307\/."},{"key":"e_1_2_11_18_1","unstructured":"ClinicalTrials.gov A Study to Evaluate the Effect of Food on the Pharmacokinetics of VX\u2010548 ClinicalTrials.govIdentifier: NCT05851157 accessed July 10 2025 https:\/\/clinicaltrials.gov\/study\/NCT05851157."},{"key":"e_1_2_11_19_1","unstructured":"ClinicalTrials.gov Evaluation of the Pharmacokinetics and Safety of VX\u2010548 in Participants With Renal Impairment ClinicalTrials.govIdentifier: NCT05704556 accessed July 10 2025 https:\/\/clinicaltrials.gov\/study\/NCT05704556\/."},{"key":"e_1_2_11_20_1","unstructured":"ClinicalTrials.gov Evaluation of the Effects of Omeprazole and Rifampin on the Pharmacokinetics of VX\u2010548 in Healthy Participants ClinicalTrials.govIdentifier: NCT05635110 accessed July 10 2025 https:\/\/clinicaltrials.gov\/study\/NCT05635110."},{"key":"e_1_2_11_21_1","unstructured":"ClinicalTrials.gov Evaluation of the Pharmacokinetics and Safety of VX\u2010548 in Participants With Mild or Moderate Hepatic Impairment ClinicalTrials.govIdentifier: NCT05560464 accessed July 10 2025 https:\/\/clinicaltrials.gov\/study\/NCT05560464."},{"key":"e_1_2_11_22_1","unstructured":"ClinicalTrials.gov A Study to Evaluate the Pharmacokinetic Drug\u2010drug Interactions Between VX\u2010548 Midazolam and Digoxin ClinicalTrials.govIdentifier: NCT05541471 accessed July 10 2025 https:\/\/clinicaltrials.gov\/study\/NCT05541471."},{"key":"e_1_2_11_23_1","unstructured":"Medscape Journavx (Suzetrigine) \u2013 Drug Monograph. Medscape accessed June 12 2025 https:\/\/reference.medscape.com\/drug\/journavx\u2010suzetrigine\u20104000474#10."},{"key":"e_1_2_11_24_1","unstructured":"U.S. Food and Drug Administration JOURNAVX (Suzetrigine) Tablets for Oral Use: Prescribing Information accessed June 12 2025 https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2025\/219209s000lbl.pdf."},{"key":"e_1_2_11_25_1","unstructured":"Institute for Clinical and Economic Review \u201cSuzetrigine for Acute Pain: Draft EvidenceReport \u201d (2024) accessed June 12 2025 https:\/\/icer.org\/wp\u2010content\/uploads\/2024\/12\/ICER_Acute\u2010Pain_Draft\u2010Report_For\u2010Publication_120924.pdf."},{"key":"e_1_2_11_26_1","unstructured":"ClinicalTrials.gov Evaluation of Efficacy and Safety of Suzetrigine for Pain Associated With Diabetic Peripheral Neuropathy (VX24\u2010548\u2010110) ClinicalTrials.govIdentifier: NCT06628908 accessed June 12 2025 https:\/\/clinicaltrials.gov\/study\/NCT06628908."},{"key":"e_1_2_11_27_1","unstructured":"ClinicalTrials.gov Evaluation of the Long\u2010term Safety and Effectiveness of Suzetrigine (SUZ) in Participants With Painful Diabetic Peripheral Neuropathy (DPN) ClinicalTrials.govIdentifier: NCT06696443 accessed June 12 2025 https:\/\/clinicaltrials.gov\/study\/NCT06696443."},{"key":"e_1_2_11_28_1","volume-title":"Vertex Presents Positive Results From Phase 2 Study of VX\u2010548 in Painful Diabetic Peripheral Neuropathy","author":"Vertex Pharmaceuticals Incorporated","year":"2023"},{"key":"e_1_2_11_29_1","unstructured":"ClinicalTrials.gov A Phase 4 Open\u2010label Single\u2010arm Study Evaluating the Effectiveness and Safety of Suzetrigine (SUZ) for Acute Pain After Selected Surgeries ClinicalTrials.govIdentifier: NCT06887959 accessed June 12 2025 https:\/\/clinicaltrials.gov\/study\/NCT06887959."},{"key":"e_1_2_11_30_1","unstructured":"ClinicalTrials.gov A Single\u2010Arm Study Evaluating the Effectiveness and Safety of Suzetrigine (SUZ) for Acute Pain After Aesthetic or Reconstructive Surgeries (VX24\u2010548\u2010113) ClinicalTrials.govIdentifier: NCT06887972 accessed June 12 2025 https:\/\/clinicaltrials.gov\/study\/NCT06887972."}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70414","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T10:42:27Z","timestamp":1763980947000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.70414"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":29,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1111\/cts.70414"],"URL":"https:\/\/doi.org\/10.1111\/cts.70414","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11]]},"assertion":[{"value":"2025-07-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70414"}}