Suzetrigine

Suzetrigine
Names
Trade namesJournavx
Other namesVX-548
IUPAC name
  • 4-[[(2R,3S,4S,5R)-3-(3,4-Difluoro-2-methoxyphenyl)-4,5-dimethyl-5-(trifluoromethyl)oxolane-2-carbonyl]amino]pyridine-2-carboxamide
Clinical data
Drug classSodium channel blocker[1]
Main usesPain[1]
Side effectsItching, muscle spasms, increased blood creatine kinase, rash[2]
InteractionsGrapefruit, some birth control[2][1]
Routes of
use		By mouth[1]
Typical dose50 mg BID[1]
Legal
License data
Legal status
Chemical and physical data
FormulaC21H20F5N3O4
Molar mass473.400 g·mol−1
3D model (JSmol)
SMILES
  • CC1C(C(OC1(C)C(F)(F)F)C(=O)NC2=CC(=NC=C2)C(=O)N)C3=C(C(=C(C=C3)F)F)OC
InChI
  • 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 a non-opioid pain medication.[1][2] Specifically it is used for moderate to severe pain of short duration.[1] It is beleived to avoid the addictive concerns of opioids.[3] It is taken by mouth.[1]

Common side effects include itching, muscle spasms, increased blood creatine kinase, and rash.[2] It should not be used in people with significant liver problems.[1] It should not be used with grapefruit or stronge CYP3A inhibitors.[2] It may also affect the function of certain types of hormonal birth control.[1] It works by altering pain-signaling pathway involving sodium channels in the peripheral nervous system.[2]

Suzetrigine was approved for medical use in the United States in 2025.[2] The proposed wholesale cost as of 2025 is 15.50 USD per dose which is taken twice per day.[4][1] It was developed by Vertex Pharmaceuticals.[3]

Medical uses

Suzetrigine is used to treat moderate to severe pain in adults of short duration.[1][2] It is unknown if it is useful for chronic pain as of January 2025, having not been studied beyond two weeks.[3][1] Use in children has not been studied.[4]

Efficacy

It reduces acute pain typically from seven to four on the standard numerical scale used to rate pain.[5][6] This is similar to a combination of hydrocodone and acetaminophen.[6][7] It was not found to be useful in a trial of pain from sciatica.[4]

It is claimed that this is without the risks of addiction, sedation, or overdose.[8] Some are skeptical of this claim.[3]

The efficacy was evaluated in two randomized trials of acute surgical pain, one following abdominoplasty and another following bunionectomy.[2] Both trials found that it reduced pain more effectively than a placebo.[2]

Dose

It is generally used as 100 mg followed by 50 mg every 12 hours.[1]

Side effects

Common side effects include itching, rash, muscle spasms, and increased levels of creatine kinase.[2] Mild side effects may include nausea, constipation, headache, and dizziness.[5][6] As of 2024, long-term safety and side effects remain undetermined.[6]

In preliminary research, suzetrigine had no serious neurological, behavioral, or cardiovascular effects.[9]

Interactions

Concomitant use of suzetrigine with strong CYP3A inhibitors is contraindicated.[1][2] Consuming grapefruit may cause a grapefruit–drug interaction via a CYP3A mechanism.[2]

Mechanism of action

It is a small-molecule that works as a selective inhibitor of Nav1.8-dependent pain-signaling pathways in the peripheral nervous system,[9][10]

It is claimed to avoid the addictive potential of opioids which affect the central nervous system.[9][10][5] Unlike opioid medications, which reduce pain signals in the brain, suzetrigine works by closing sodium channels in peripheral nerves, inhibiting pain-signaling nerves from transmitting painful sensations to the brain.[9][10][5]

In pharmacological studies, suzetrigine selectively inhibited Nav1.8 channels, but not other voltage-gated sodium channels, and bound to a unique site on these sodium channels with a novel allosteric mechanism.[9]

History

Vertex Pharmaceuticals announced in January 2024 that suzetrigine had successfully met several endpoints in its phase III clinical trials.[11] The company announced in July 2024 that the US Food and Drug Administration (FDA) had accepted a new drug application for suzetrigine.[12] The FDA granted the application for suzetrigine priority review, fast track, and breakthrough therapy designations for the treatment of moderate-to-severe acute pain.[12]

Suzetrigine is the first medication to be approved by the US Food and Drug Administration (FDA) in this new class of pain management medicines.[2]

Society and culture

Legal status

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

Names

Suzetrigine is the international nonproprietary name.[13] It is sold under the brand name Journavx.[1][2]

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 "Journavx (suzetrigine) tablets, for oral use: HIGHLIGHTS OF PRESCRIBING INFORMATION" (PDF). Vertex Pharmaceuticals Incorporated. 30 January 2025. Archived (PDF) from the original on 31 January 2025. Retrieved 31 January 2025. Initial U.S. Approval 2025
  2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 "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 31 January 2025. Retrieved 30 January 2025. Public Domain This article incorporates text from this source, which is in the public domain.
  3. ↑ 3.0 3.1 3.2 3.3 Gilbert, Daniel (13 January 2025). "Billed as nonaddictive, new pain pill could soon win FDA approval". Washington Post. Archived from the original on 14 January 2025. Retrieved 2 February 2025.
  4. ↑ 4.0 4.1 4.2 Gilbert, Daniel (January 30, 2025). "FDA approves new, non-opioid painkiller Journavx". Retrieved 2 February 2025.
  5. ↑ 5.0 5.1 5.2 5.3 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.
  6. ↑ 6.0 6.1 6.2 6.3 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. PMID 39552600.
  7. ↑ Kingwell, Katie (December 2024). "NaV1.8 inhibitor poised to provide opioid-free pain relief". Nature Reviews. Drug Discovery. 24 (1): 3–5. doi:10.1038/d41573-024-00203-3. PMID 39668193.
  8. ↑ Dolgin, Elie (2025-01-31). "US drug agency approves potent painkiller — the first non-opioid in decades". Nature. doi:10.1038/d41586-025-00274-1. ISSN 1476-4687. Archived from the original on 2025-02-01. Retrieved 2025-01-31.
  9. ↑ 9.0 9.1 9.2 9.3 9.4 Osteen, Jeremiah D.; Immani, Swapna; Tapley, Tim L.; Indersmitten, Tim; Hurst, Nicole W.; Healey, Tiffany; Aertgeerts, Kathleen; Negulescu, Paul A.; Lechner, Sandra M. (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. doi:10.1007/s40122-024-00697-0. PMID 39775738.
  10. ↑ 10.0 10.1 10.2 Jones, Jim; Correll, Darin J.; Lechner, Sandra M; Jazic, Ina; Miao, Xiaopeng; Shaw, David; Simard, Christopher; Osteen, Jeremiah D.; Hare, Brian; Beaton, Alina; Bertoch, Todd; Buvanendran, Asokumar; Habib, Ashraf S.; Pizzi, Lois J.; Pollak, Richard A.; Weiner, Scott G.; Bozic, Carmen; Negulescu, Paul; White, Paul F. (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.
  11. ↑ "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.
  12. ↑ 12.0 12.1 "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.
  13. ↑ World Health Organization (2023). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 90". WHO Drug Information. 37 (3). hdl:10665/373341.

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