By William Elliott, MD, FACP, and James Chan, PharmD, PhD
The U.S. Food and Drug Administration has approved suzetrigine, a first-in-class, non-opioid analgesic, to treat moderate to severe pain. Suzetrigine is a potent and selective peripheral sodium channel blocker.1,2 It received Fast Track, accelerated priority review, and breakthrough therapy designation.3 Suzetrigine is distributed by Vertex Pharmaceuticals Incorporated as Journavx.
Indications
Suzetrigine is indicated for the treatment of moderate to severe acute pain in adults.1
Dosage
The recommended initial dose is 100 mg (two 50-mg tablets) taken on an empty stomach at least one hour before or two hours after food.1 Clear liquid, such as water, apple juice, vegetable broth, tea, or black coffee may be consumed. Starting 12 hours after the initial dose, a 50-mg tablet is taken every 12 hours with or without food. Food or drink containing grapefruit juice should be avoided. Suzetrigine is available as 50-mg tablets.
Potential Advantages
Suzetrigine is the first-in-class non-opioid analgesic that acts selectively on NaV1.8, a sodium channel-mediated pain-signaling pathway only found in the peripheral nervous system.1,2 In contrast, local anesthetics are nonselective NaV blockers.2 Suzetrigine does not appear to have potential for addiction or dependance, since NaV1.8 is not expressed in the central nervous system (i.e., the brain or spinal cord).2
Potential Disadvantages
Suzetrigine appears to be less effective than hydrocodone/acetaminophen (HB/APAP) in relieving moderate to severe hard tissue pain following bunionectomy.1 Suzetrigine is an inducer of CYP3A as well as a substrate for CYP3A. Strong and moderate inhibitors increase suzetrigine and its active metabolite (M6-SUZ). Concomitant use with strong CYP3A inhibitors is contraindicated, and the dose needs to be reduced with moderate inhibitors.1 Use with strong or moderate CYP3A inducers should be avoided. Sensitive substrates of CYP3A may lose efficacy with concomitant administration with suzetrigine.1
Elevation of creatine phosphokinase (more than three times the upper limit of normal) occurred in 2.9% of suzetrigine-treated study participants, compared to 1.2% of placebo-treated participants.1 Decrease in estimated glomerular filtration rate occurred in 2.5% vs. 0.9% of those patients, respectively. Patients using hormonal contraceptives other than levonorgestrel and norethindrone should use an additional nonhormonal contraceptive or use alternative contraceptives during suzetrigine treatment and for 28 days after discontinuation.1
Comments
Suzetrigine is a selective blocker of the NaV1.8 voltage-gated sodium channels.1 These are expressed in peripheral dorsal root ganglion sensory neurons, and suzetrigine’s action inhibits transmission of pain signals to the spinal cord and brain. Its efficacy was established in two randomized, double-blind, placebo-controlled trials of acute pain.1 One followed full abdominoplasty (trial 1), and the other followed bunionectomy (trial 2). In trial 1, adult participants with moderate to severe acute pain were randomized to suzetrigine (n = 447), placebo (n = 223), and hydrocodone bitartrate/acetaminophen (n = 448). The mean age of the participants was 42 years, 98% were female, and 70% were white, with a mean pain score at baseline of 7.4 (range, 4 to 10). Efficacy was evaluated by the time-weighted sum of the pain intensity difference from 0 to 48 hours (SPID48) in the suzetrigine group compared to the placebo group and then to the HB/APAP group. Suzetrigine was superior to placebo and comparable to HB/APAP in relieving post-operative soft tissue pain from abdominoplasty. In trial 2, suzetrigine (n = 426) was superior to placebo (n = 216) but less effective than HB/APAP (n = 431) in relieving hard tissue pain from bunionectomy.1
Clinical Implications
Pain is a common medical problem. Vertex Pharmaceuticals estimated that 80 million Americans receive prescriptions for moderate to severe pain each year.4 Acute short-term pain (less than one month) generally is caused by tissue trauma or injury (e.g., postoperative pain) and typically is treated with acetaminophen, nonsteroidal anti-inflammatory agents (NSAIDs), and the often-prescribed HB/APAP combination.5
Nonopioid therapies are at least as effective as opioids for many common acute pain conditions, including low back pain, neck pain, pain related to other musculoskeletal injuries (e.g., sprains, strains, tendonitis, and bursitis), pain related to minor surgeries typically associated with minimal tissue injury and mild postoperative pain (e.g., simple dental extraction), dental pain, kidney stone pain, and headaches, including episodic migraines.6
The introduction of a non-opioid analgesic provides a potentially important addition to acute pain management. There are no published trials between suzetrigine and APAP or NSAIDs. Compared to HB/APAP, suzetrigine is comparable to or less effective, depending on the type of pain model studied (i.e., soft tissue or hard tissue pain). Bunionectomay may have higher assay sensitivity than soft tissue surgery models.7 The cost of suzetrigine is $15.50 per 50-mg tablet, or $420 for a two-week course.
References
- Vertex Pharmaceuticals Incorporated. Journavx prescribing information. Revised January 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/219209s000lbl.pdf
- Osteen JD, Immani S, Tapley TL, et al. 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 Ther. 2025; Jan 8. doi:10,1007/s-40122-024-00697-0. [Online ahead of print].
- U.S. Food and Drug Administration. FDA approves novel non-opioid treatment for moderate to severe acute pain. Published Jan. 30, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-novel-non-opioid-treatment-moderate-severe-acute-pain
- Vertex Pharmaceuticals Incorporated. Vertex announces FDA approval of Journavx (suzetrigine), a first-in-class treatment for adults with moderate-to-severe acute pain. Published Jan. 30, 2025. https://news.vrtx.com/news-releases/news-release-details/vertex-announces-fda-approval-journavxtm-suzetrigine-first-class
- Definitive Healthcare. Top 10 most common pain medications. Published Jan. 31, 2025. https://www.definitivehc.com/resources/healthcare-insights/most-common-pain-medication
- Centers for Disease Control and Prevention. Nonopioid therapies for pain management. Jan. 31, 2025. https://www.cdc.gov/overdose-prevention/hcp/clinical-care/nonopioid-therapies-for-pain-management.html
- Singla NK, Desjardins PJ, Chang PD. A comparison of the clinical and experimental characteristics of four acute surgical pain models: Dental extraction, bunionectomy, joint replacement, and soft tissue surgery. Pain. 2014;155(3):441-456.
The U.S. Food and Drug Administration has approved suzetrigine, a first-in-class, non-opioid analgesic, to treat moderate to severe pain.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content