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-{{#parsoidfragment:6}}(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]

If one dose is missed, the intended missed dose should be taken as soon as possible, while if more than one dose is missed, 100 milligrams is to be taken as soon as possible, both followed by another at the recommended time. [8] For patients with moderate hepatic impairment or taking CYP3A inhibitors, the missed dose should be taken as soon as possible followed by subsequent doses at the scheduled time, unless the next dose is within 6 hours, in which that one should be skipped. [8]

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. [11] Medical professionals have noted its efficacy may be inferior to high-dose opioid analgesics. [12] 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. [13] 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] [14]

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] [13] 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. [15] Due to its novel mechanism, the FDA granted priority review, fast track, and breakthrough therapy designations to the application for suzetrigine. [2] [15] 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] [16]

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 [17] .

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). [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 118326. doi:10.1016/j.ejmech.2025.118326. ISSN   0223-5234.
  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 4 5 "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. ↑ 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.
  12. ↑ 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.
  13. 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.
  14. ↑ 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.
  15. 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.
  16. ↑ 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.
  17. ↑ 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.
  18. ↑ "Lobbying Update: $1,140,000 of VERTEX PHARMACEUTICALS INCORPORATED lobbying was just disclosed". Nasdaq. 16 July 2025. Retrieved 15 August 2025.

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