Suzetrigine

Last updated

Suzetrigine
Suzetrigine.svg
Suzetrigine 3D structure.png
Clinical data
Pronunciation /suˈzɛtrɪdʒiːn/
soo-ZE-tri-jeen
Trade names Journavx
Other namesVX-548
AHFS/Drugs.com Monograph
MedlinePlus a625039
License data
Routes of
administration 		By mouth
Drug class Nav1.8 sodium channel blocker; analgesic
ATC code
  • None
Legal status
Legal status
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
Formula C21H20F5N3O4
Molar mass 473.400 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 oral medication used for moderate to severe acute pain management in adults. [1] [2] It 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. [3] [4] Nav1.8 channels are predominantly present in peripheral nociceptive neurons of the dorsal root ganglia. [4] [5] Suzetrigine inhibits pain signals before they reach the central nervous system and has no addictive potential. [3] [6]

Contents

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

Suzetrigine was developed by Vertex Pharmaceuticals. [7] It was approved for medical use in the United States on January 30, 2025. [2] [8] Due to Suzetrigine's novel mechanism of action, it is the first medication to be approved by the US Food and Drug Administration (FDA) in the non-opioid class of medications for the treatment of moderate-to-severe acute pain. [2] [5]

Medical uses

Suzetrigine is indicated for the treatment of moderate to severe acute pain in adults. [1] [2]

Dosage and administration

Suzetrigine is dispensed as 50 milligram oral tablets that are to be swallowed whole and not crushed or chewed. [1] [2] To avoid a delay of onset, it is recommended to begin taking a starting dose of 100 mg on an empty stomach. [6] Following the initial dose, 50 mg is to be taken every 12 hours for the shortest possible duration. [1] For those with moderate hepatic impairment, 50 mg doses are to be taken 24 hours apart following the fifth dose. [1]

Contraindications

Concomitant use of suzetrigine with strong CYP3A4 inhibitors is contraindicated. [1] [2] When taken with moderate CYP3A inhibitors, dose adjustments are required. [5] While taking suzetrigine, and for 28 days after use has ended, those taking hormonal contraceptives with progesterone's other than levonorgestrel and norethindrone should use additional or an alternative non-hormonal contraceptive. [8]

Individuals with severe hepatic impairment (Child-Pugh Class C) should not take suzetrigine. [1] [8]

Adverse effects

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. [3]

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

Interactions

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

Mechanism of action

Suzetrigine operates on Nav1.8 channels predominately found in the peripheral nociceptive neurons of the dorsal root ganglia. [3] [4] 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. [3] [4] [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. [3] [11] Suzetrigine selectively bound to this site on these sodium channels with a novel allosteric mechanism, thereby stabilizing the closed state and causing tonic inhibition. [3]

History

Vertex Pharmaceuticals announced in January 2024 that suzetrigine had successfully met several endpoints in its Phase III clinical trials. [7] The company announced in July 2024 that the FDA had accepted a New Drug Application for suzetrigine. [12] Due to its novel mechanism, the FDA granted priority review, fast track, and breakthrough therapy designations to the application for suzetrigine. [2] [12] 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] [13]

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 [14] .

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). [15]

Research

Treatment of acute pain using suzetrigine has not been studied beyond 14 days of use. [1]

Efficacy

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]

However, in clinical studies, no superiority over hydrocodone and paracetamol (acetaminophen) in terms of pain reduction was shown over 48 hours. [16] Medical professionals have noted its efficacy may be inferior to high-dose opioid analgesics. [17] 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. [11] Moreover, usage has not been studied in those younger than 18 or older than 80 years of age and its cost-effectiveness is disputed. [7] [18]

References

  1. 1 2 3 4 5 6 7 8 9 10 11 "Journavx- suzetrigine tablet, film coated". DailyMed. 6 February 2025. Archived from the original on 3 April 2025. Retrieved 2 April 2025.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 13 "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.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  3. 1 2 3 4 5 6 7 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.
  4. 1 2 3 4 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.
  5. 1 2 3 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.
  6. 1 2 "Suzetrigine". go.drugbank.com. Retrieved 16 November 2025.
  7. 1 2 3 "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.
  8. 1 2 3 "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.
  9. 1 2 3 4 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. 1 2 3 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. 1 2 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.
  12. 1 2 "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. Retrieved 31 January 2025– via Business Wire.
  13. ↑ 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.
  14. ↑ 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 (Report). clinicaltrials.gov.
  15. ↑ "Lobbying Update: $1,140,000 of VERTEX PHARMACEUTICALS INCORPORATED lobbying was just disclosed". Nasdaq. 16 July 2025. Retrieved 15 August 2025.
  16. ↑ 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.
  17. ↑ 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.
  18. ↑ 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.

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