USHP Winter Newsletter 2026

Suzetrigine

by Katie Anderton, PharmD Candidate 2028

On January 30, 2025, the FDA approved suzetrigine (Journavx™; Vertex Pharmaceuticals, formerly VX-548), a first-in-class non-opioid analgesic for the treatment of moderate to severe pain in adults [1,2].  The mechanism of action for this new drug is a voltage-gated sodium channel blocker (NaV1.8), a channel expressed in peripheral sensory neurons but not the brain [1,3]. This article will highlight the efficacy, safety, and important clinical insights related to suzetrigine.

History

Prior to the approval of suzetrigine, the most recent non-opioid medication approved for pain management by the FDA was celecoxib, approved over 20 years ago in 1998 [5].  Targeting selective sodium channels was not a novel idea for the development of suzetrigine; it has been proposed as a mechanism in the pharmacy world since the early 2000s [6].  With the continuation of the opioid epidemic, suzetrigine’s approval offers a potential non-addictive solution for pain management. 

Efficacy and Safety

The efficacy of suzetrigine for moderate-to-severe pain has been studied in the NAVIGATE 1 and NAVIGATE 2 trials [3].  In these phase 3, randomized, double-blind, placebo- and active-controlled trials (NAVIGATE 1, NAVIGATE 2), adults ages 18-80 years with moderate-severe pain post bunionectomy or abdominoplasty were given suzetrigine (100 mg, then 50 mg every 12 hours) to determine the primary outcome of time-weighted sum of pain intensity difference over 48 hours (SPID48) compared to placebo [7].  Secondary endpoints included SPID48 when comparing suzetrigine (100 mg, then 50 mg every 12 hours) to hydrocodone-bitartrate acetaminophen (HB/APAP; 5/325 mg every 6 h) following either a bunionectomy or abdominoplasty over 14 days [7]. Both trials were statistically significant for the primary outcome, showing that suzetrigine was superior to placebo [1,7].  Neither of these studies were statistically significant for the secondary endpoint of suzetrigine being superior to HB/APAP [7].

A limitation of the study was that participants were allowed to receive ibuprofen for additional pain management, of which ~80% required this additional supplementation.  However, an imputation analysis of suzetrigine's effect without ibuprofen was included to estimate the true effect of suzetrigine.  These studies showed that suzetrigine is well tolerated, with minimal side effects [7]. The most common side effects in patients treated with suzetrigine include itching, muscle spasms, increased creatine phosphokinase levels, and rash [1,7].   However, it is unclear if more side effects will appear as this medication is utilized more in practice or for longer-term pain control.

Dosing and Administration

The recommended dosing is a 100mg loading dose followed by 50mg every 12 hours after.1  The onset of suzetrigine is between 2-4 hours, supporting that the timing of this medication is crucial and may not be used for breakthrough pain [1].  Suzetrigine has not been studied for its effect after 14 days, thus supporting the manufacturer's and FDA's recommendations to use for a short duration, as consistent with patient goals [1,2].  Suzetrigine is to be stored at room temperature (68°F to 77°F) [1].

Other Considerations

Use of suzetrigine in combination with strong CYP3A4 inhibitors (including grapefruit-containing foods or drinks) is contraindicated due to the risk of elevated plasma concentrations and associated adverse effects. Moderate CYP3A4 inhibitors also increase exposure and require a dose reduction of suzetrigine [1,2].  Conversely, strong CYP3A4 inducers may lower plasma concentrations of suzetrigine, resulting in treatment failure. In addition, suzetrigine may impact the effectiveness of hormonal contraceptives containing progestins other than levonorgestrel or norethindrone; for this reason, patients should use backup contraceptives while taking suzetrigine and for 28 days after. Currently, the cash price for suzetrigine is approximately $15 per tablet, which is considerably higher than other analgesics [5].

Summary

The approval of a first-in-class medication marks an important development in pain management. With increasing clinical experience, the incorporation of suzetrigine as a non-addictive analgesic may warrant further consideration; however, its use may be limited by a lack of robust outcomes data and high acquisition price.

References

1. FDA. Journavx Package Insert. U.S. Food and Drug Administration. Published January 30, 2025. chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/219209s000lbl.pdf

2. FDA. FDA Approves Novel Non-Opioid Treatment for Moderate to Severe Acute Pain. U.S. Food and Drug Administration. Published January 30, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-novel-non-opioid-treatment-moderate-severe-acute-pain 

3. Vertex Announces FDA Acceptance of New Drug Application for Suzetrigine for the Treatment of Moderate-to-Severe Acute Pain | Vertex Pharmaceuticals Newsroom. Vertex Pharmaceuticals Newsroom. Published 2024. https://news.vrtx.com/news-releases/news-release-details/vertex-announces-fda-acceptance-new-drug-application-suzetrigine

4. Keam, S.J. Suzetrigine: First Approval. Drugs 85, 845–851 (2025). https://doi.org/10.1007/s40265-025-02178-w

5. Kramer KJ. Suzetrigine – A Novel Analgesic Emerges. Anesth Prog. 2025;72(2):63-64. Published 2025 Jun 9. doi:10.2344/Editorial_72_2

6. Eagles DA, Chow CY, King GF. Fifteen years of NaV 1.7 channels as an analgesic target: Why has excellent in vitro pharmacology not translated into in vivo analgesic efficacy?. Br J Pharmacol. 2022;179(14):3592-3611. doi:10.1111/bph.15327

7. Bertoch T, D'Aunno D, McCoun J, et al. Suzetrigine, a Nonopioid Na V 1.8 Inhibitor for Treatment of Moderate-to-severe Acute Pain: Two Phase 3 Randomized Clinical Trials. Anesthesiology. 2025;142(6):1085-1099. doi:10.1097/ALN.0000000000005460