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Suzetrigine

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Suzetrigine
Clinical data
Pronunciation/suˈzɛtrɪdʒiːn/
soo-ZE-tri-jeen
Trade namesJournavx
Other namesVX-548; VX548
AHFS/Drugs.comMonograph
MedlinePlusa625039
License data
Routes of
administration		Oral[1]
Drug classNav1.8 sodium channel blocker; analgesic
ATC code
  • None
Legal status
Legal status
Pharmacokinetic data
BioavailabilityUnknown[1]
Protein binding99%[1]
MetabolismCYP3A4[1]
MetabolitesM6-SUZ (active)[1]
Onset of action3.0 hours (TmaxTooltip time to peak levels)[1]
Elimination half-lifeSuzetrigine: 23.6 hours[1]
M6-SUZ: 33.0 hours[1]
ExcretionFeces: 49.9%[1]
Urine: 44.0%[1]
Identifiers
  • 4-[[(2R,3S,4S,5R)-3-(3,4-Difluoro-2-methoxyphenyl)-4,5-dimethyl-5-(trifluoromethyl)oxolane-2-carbonyl]amino]pyridine-2-carboxamide
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC21H20F5N3O4
Molar mass473.400 g·mol−1
3D model (JSmol)
  • COc1c([C@H]2[C@H](C(=O)Nc3ccnc(C(N)=O)c3)O[C@@](C)(C(F)(F)F)[C@H]2C)ccc(F)c1F
  • InChI=1S/C21H20F5N3O4/c1-9-14(11-4-5-12(22)15(23)16(11)32-3)17(33-20(9,2)21(24,25)26)19(31)29-10-6-7-28-13(8-10)18(27)30/h4-9,14,17H,1-3H3,(H2,27,30)(H,28,29,31)/t9-,14-,17-,20-/m0/s1
  • Key:XSQUJFKRXZMOKA-PAFIKIDNSA-N

Suzetrigine, sold under the brand name Journavx, is an analgesic medication used in the treatment of moderate to severe acute pain.[1][2] It is taken orally.[1] Suzetrigine was developed by Vertex Pharmaceuticals.[3]

The most common adverse effects include itching, muscle spasms, increased blood level of creatine phosphokinase, and rash.[1][2]

Suzetrigine is a small-molecule non-opioid analgesic that works as a selective inhibitor of Nav1.8-dependent pain-signaling pathways in the peripheral nervous system.[4][5] Nav1.8 channels are predominantly present in peripheral nociceptive neurons of the dorsal root ganglia.[5][6] Suzetrigine inhibits pain signals before they reach the central nervous system and has no addictive potential.[4]

Suzetrigine was approved for medical use in the United States in January 2025.[2][7] The US Food and Drug Administration considers it to be a first-in-class medication.[2][7][8]

Medical uses

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Suzetrigine is indicated for the treatment of moderate to severe acute pain in adults.[1][2] It was primarily studied in people with postoperative pain, including due to abdominoplasty and bunionectomy.[1] However, a small minority of patients received suzetrigine for non-surgical pain, including arthralgias, limb pain, and sprains and strains.[1] Treatment of acute pain using suzetrigine has not been studied beyond 14 days of use.[1]

In clinical studies conducted through 2024, suzetrigine reduced pain typically from 7 to 4 on the standard numeric scale used to rate pain.[9][10] The efficacy of suzetrigine was evaluated in two randomized, double-blind, placebo- and active-controlled trials of acute surgical pain, one following abdominoplasty and the other following bunionectomy.[2] Both trials found that suzetrigine reduced pain more effectively than placebo.[2] Suzetrigine was not superior to placebo for the treatment of lumbosacral radiculopathy.[11]

However, in clinical studies, no superiority over hydrocodone and paracetamol (acetaminophen) in terms of pain reduction was shown over 48 hours.[12] Medical professionals have noted its efficacy may be inferior to high-dose opioid analgesics.[13] There are no studies comparing suzetrigine with high-dose opioids. Suzetrigine exhibits CYP3A4-mediated drug interactions and there is limited long-term data regarding its use.[14] Moreover, usage has not been studied in those younger than 18 or older than 80 years of age and its cost-effectiveness is disputed.[3][15]

Contraindications

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Concomitant use of suzetrigine with strong CYP3A4 inhibitors is contraindicated.[1][2]

Adverse effects

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The most common adverse effects of suzetrigine may include itching, rash, muscle spasms, and increased levels of creatine kinase.[2] Mild side effects may include nausea, vomiting, constipation, headache, and dizziness.[9][10] In preliminary research, suzetrigine had no serious neurological, behavioral, addictive or cardiovascular effects.[4]

As of 2024, long-term safety in broader contexts including multimodal analgesia, pregnancy and breastfeeding women remain undetermined.[10]

Interactions

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Consuming grapefruit while using suzetrigine may cause adverse grapefruit–drug interactions.[1][2]

Pharmacology

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Pharmacodynamics

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Suzetrigine operates on Nav1.8 channels predominately found in the peripheral nociceptive neurons of the dorsal root ganglia.[4][5] This mechanism avoids the addictive potential of opioids caused by their effects on the reward system in the central nervous system.[9] Unlike opioid medications, which reduce pain signals in the brain, suzetrigine works by closing sodium channels in peripheral nerves, inhibiting painful sensations from being transmitted to the brain.[4][5][9]

In pharmacological studies, suzetrigine bound to the voltage-sensing domain 2 of Nav1.8 channels with a 3,100-times greater affinity than to other voltage-gated sodium channels.[4][14] Suzetrigine selectively bound to this site on these sodium channels with a novel allosteric mechanism, thereby stabilizing the closed state and causing tonic inhibition.[4]

Pharmacokinetics

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Suzetrigine is well-absorbed from the GI tract, with the 50mg maintenance dose being relatively unaffected by meal timing, and the 100mg initial dose requiring an empty stomach for proper absorption. Suzetrigine has a mean effective half-life of 23.6 hours and is 99% protein-bound; its active metabolite, M6-SUZ, has a mean effective half-life of 33 hours and is 96% protein-bound.[16] Steady-state concentrations are reached within 3 days.[17] The primary metabolic pathway is via CYP3A isozymes, followed by excretion via feces (49.9%) and urine (44%).[16]

Suzetrigine may potentially interact with certain hormonal birth controls, resulting in reduced efficacy. During clinical trials, it was observed that the efficacy of levonorgestrel and ethinyl estradiol were not reduced by suzetrigine administration, and can be safely used together.[16]

History

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Vertex Pharmaceuticals announced in January 2024 that suzetrigine had successfully met several endpoints in its phase III clinical trials.[3] The company announced in July 2024 that the US Food and Drug Administration (FDA) had accepted a New Drug Application for suzetrigine.[18] Due to its novel mechanism, the FDA granted priority review, fast track, and breakthrough therapy designations to the application for suzetrigine.[2][18] In January 2025, the FDA granted approval of Journavx to Vertex Pharmaceuticals, making it the first non-opioid pain medication to be approved by the FDA in two decades.[2][19]

As of November 2025, phase IV post-marketing clinical trials are underway to assess the effectiveness and safety of suzetrigine as a part of multimodal therapy for the treatment of acute post-operative pain.[20]

The manufacturer engaged in lobbying activity promoting non-opioid pain treatment and supporting the NO PAIN Act (Non-Opioids Prevent Addiction In the Nation Act).[21]

Society and culture

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[edit]

Suzetrigine was approved for medical use in the United States in January 2025.[1][2]

Names

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Suzetrigine is the international nonproprietary name.[22]

Suzetrigine is sold under the brand name Journavx.[1][2]

References

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  1. ^ a b c d e f g h i j k l m n o p q r s t u v "Journavx- suzetrigine tablet, film coated". DailyMed. 6 February 2025. Archived from the original on 3 April 2025. Retrieved 2 April 2025.
  2. ^ a b c d e f g h i j k l m n "FDA Approves Novel Non-Opioid Treatment for Moderate to Severe Acute Pain" (Press release). U.S. Food and Drug Administration (FDA). 30 January 2025. Archived from the original on 7 February 2025. Retrieved 30 January 2025. Public Domain This article incorporates text from this source, which is in the public domain.
  3. ^ a b c "Vertex Announces Positive Results From the VX-548 Phase 3 Program for the Treatment of Moderate-to-Severe Acute Pain" (Press release). Vertex. 30 January 2024. Archived from the original on 25 December 2024. Retrieved 31 January 2025 – via Business Wire.
  4. ^ a b c d e f g Osteen, Jeremiah D.; Immani, Swapna; Tapley, Tim L.; Indersmitten, Tim; Hurst, Nicole W.; Healey, Tiffany; et al. (January 2025). "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 and Therapy. 14 (2): 655–674. doi:10.1007/s40122-024-00697-0. PMC 11914629. PMID 39775738.
  5. ^ a b c d Jones, Jim; Correll, Darin J.; Lechner, Sandra M; Jazic, Ina; Miao, Xiaopeng; Shaw, David; et al. (August 2023). "Selective Inhibition of NaV1.8 with VX-548 for Acute Pain". The New England Journal of Medicine. 389 (5): 393–405. doi:10.1056/NEJMoa2209870. PMID 37530822. S2CID 260377748.
  6. ^ Wu, Zhixing; Lu, Dai (15 January 2026). "Advances in the discovery of selective NaV1.8 inhibitors for pain management". European Journal of Medicinal Chemistry. 302 (Pt 2) 118326. doi:10.1016/j.ejmech.2025.118326. ISSN 0223-5234. PMID 41175507.
  7. ^ a b "Novel Drug Approvals for 2025". U.S. Food and Drug Administration (FDA). 21 February 2025. Archived from the original on 3 March 2025. Retrieved 9 March 2025.
  8. ^ "Advancing Health Through Innovation: New Drug Therapy Approvals 2025" (PDF). U.S. Food and Drug Administration (FDA). January 2026.
  9. ^ a b c d Broadfoot, Marla (20 August 2024). "New Painkiller Could Bring Relief to Millions — without Addiction Risk". Scientific American. Archived from the original on 30 December 2024. Retrieved 31 January 2025.
  10. ^ a b c Hang Kong, Aaron Yik; Tan, Hon Sen; Habib, Ashraf S. (September 2024). "VX-548 in the Treatment of Acute Pain". Pain Management. 14 (9): 477–486. doi:10.1080/17581869.2024.2421749. PMC 11721852. PMID 39552600.
  11. ^ "Vertex Announces Results From Phase 2 Study of Suzetrigine for the Treatment of Painful Lumbosacral Radiculopathy". 19 December 2024.
  12. ^ Bertoch, Todd; D'Aunno, Dominick; McCoun, Jessica; Solanki, Daneshvari; Taber, Louise; Urban, Joshua; et al. (21 March 2025). "Suzetrigine, a Non-Opioid NaV1.8 Inhibitor for Treatment of Moderate-to-Severe Acute Pain: Two Phase 3 Randomized Clinical Trials". Anesthesiology. 142 (6): 1085–1099. doi:10.1097/ALN.0000000000005460. ISSN 0003-3022. PMC 12061372. PMID 40117446.
  13. ^ Robinson, Christopher L.; Schatman, Michael E.; Hasoon, Jamal; Chung, Matthew; Emerick, Trent; Lo Bianco, Giuliano; et al. (2025). "Suzetrigine: Is This What We Have Been Waiting for or Just the Beginning?". Journal of Pain Research. 18: 2047–2049. doi:10.2147/JPR.S527710. ISSN 1178-7090. PMC 12009045. PMID 40255364.
  14. ^ a b Jones, Meaghan; Demery, Aryanna; Al-Horani, Rami A. (4 July 2025). "Suzetrigine: A Novel Non-Opioid Analgesic for Acute Pain Management—A Review". Drugs and Drug Candidates. 4 (3): 32. doi:10.3390/ddc4030032. ISSN 2813-2998. PMC 12337992. PMID 40799996.
  15. ^ Rind DM, McQueen B, Nikitin D, Lee W, DiStefano MJ, Zemplenyi A, et al. (31 March 2025). "Suzetrigine for Acute Pain; Final Report". Institute for Clinical and Economic Review. Archived from the original on 10 August 2025. Retrieved 15 August 2025.
  16. ^ a b c "HIGHLIGHTS OF PRESCRIBING INFORMATION, Journavx (suzetrigine) tablets, for oral use" (PDF). 2025. Archived (PDF) from the original on 1 February 2025. Retrieved 18 June 2026 – via Federal Drug Administration.
  17. ^ Pham, Andrew; Yep, Hua; Wozniak, Sebastian; Javvaji, Anisha; Nada, Eman; Bergese, Sergio (10 October 2025). "Beyond Opioids: A Review of Suzetrigine for Acute Pain Management". International Journal of Molecular Sciences. 26 (20): 9865. doi:10.3390/ijms26209865. ISSN 1422-0067. PMC 12563693. PMID 41155158.
  18. ^ a b "Vertex Announces FDA Acceptance of New Drug Application for Suzetrigine for the Treatment of Moderate-to-Severe Acute Pain" (Press release). Vertex. 30 July 2024. Archived from the original on 31 January 2025. Retrieved 31 January 2025 – via Business Wire.
  19. ^ Dolgin, Elie (January 2025). "US drug agency approves potent painkiller - the first non-opioid in decades". Nature. 638 (8050): 304–305. Bibcode:2025Natur.638..304D. doi:10.1038/d41586-025-00274-1. PMID 39885357.
  20. ^ Vertex Pharmaceuticals Incorporated (7 November 2025). A Phase 4, Open-label, Single-arm Study Evaluating the Effectiveness and Safety of Suzetrigine As Part of Multimodal Therapy for Acute Pain After Aesthetic or Reconstructive Surgeries. clinicaltrials.gov (Report).
  21. ^ "Lobbying Update: $1,140,000 of Vertex Pharmaceuticals Incorporated lobbying was just disclosed". Nasdaq. 16 July 2025. Archived from the original on 25 July 2025. Retrieved 15 August 2025.
  22. ^ World Health Organization (2023). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 90". WHO Drug Information. 37 (3). hdl:10665/373341.

Further reading

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