Suzetrigine (JOURNAVX): A Novel Drug for Acute Pain

Acute (short-term) and intense pain can result from surgery, physical trauma, or other injuries or illness. If the plausible causes have been carefully considered and addressed, pain relief is an important goal of medical treatment.[1] Delivered properly, acute-pain mitigation can reduce suffering, facilitate recovery and help prevent chronic pain.[2]

Multimodal (combination) approaches to acute pain are the standard of care.[3] Approaches include physical treatments (for example, ice, compression or elevation), talk therapies (for example, patient education or brief therapy to address anxiety about pain), and various medications, especially nonsteroidal anti-inflammatory drugs (for example, ibuprofen [ADVIL, CHILDREN’S MOTRIN, MIDOL LIQUID GELS, MOTRIN IB and generics]) and acetaminophen (TYLENOL and generics).

Opioids (for example, hydrocodone [HYSINGLA ER and generics]), although usually effective for acute and severe pain relief, have serious adverse effects (including constipation, sedation, overdose and addiction). Accordingly, research has focused on the development of new, non-opioid treatments.

In January 2025 the Food and Drug Administration (FDA) approved suzetrigine (JOURNAVX), an oral tablet for the treatment of moderate to severe acute pain in adults.[4] The initial dose is 100 mg (two 50-mg tablets), followed by a 50-mg dose 12 hours later and then 50 mg every 12 hours as needed for acute pain.

About suzetrigine

Suzetrigine is a selective sodium ion channel blocker. The medication works by blocking the flow of charged sodium atoms through nerve cell membranes, a process that results in the transmission of an electrical signal along nerve fibers.[5] Suzetrigine is designed to selectively block certain sodium ion channels that are largely in the peripheral nervous system (outside of the brain). The presumption is that this new drug can block the perception of pain while avoiding the brain-based adverse effects of opioids.

Clinical trials supporting approval[6]

The FDA approved suzetrigine based mostly on evidence from two randomized, double-blind, placebo-controlled, multi-center clinical trials. Both trials involved the treatment of moderate to severe postsurgical pain, one following abdominoplasty (“tummy tuck”) and the other following bunionectomy (big-toe bone alignment repair).

The abdominoplasty was conducted under general anesthesia with lidocaine applied immediately after the abdominal surgery. The bunionectomy was conducted under regional anesthesia (sciatic block) with intravenous sedation. Across both trials, participants were randomized to three groups: 873 were treated with suzetrigine, 879 with hydrocodone/acetaminophen and 439 with placebo. More than 85% of the participants were female.

Dosing of suzetrigine was for 48 hours, beginning with a single 100-mg dose followed by 50-mg doses every 12 hours. Parallel dosing for hydrocodone/acetaminophen was 5 mg/325 mg every six hours throughout the trial. Participants were allowed to use ibuprofen as needed if they were still in pain. During the first 48 hours, more than 80% of participants used such “rescue” ibuprofen.

The primary outcome was differences in pain scores during the first 48 hours of treatment. Pain scores were assessed using a self-reported 11-point scale where 0 means “none” and 10 means “worst pain imaginable.” Mean baseline pain score, assessed after surgery but before treatment, was 6.8 in the bunionectomy study and 7.4 in the abdominoplasty study.

All three study groups showed statistically significant reductions in pain scores. The reductions in the suzetrigine and hydrocodone/acetaminophen groups, however, were greater and roughly equivalent. For example, at 48 hours in the bunionectomy study, the mean pain score was about 3.5 with suzetrigine and 4.4 with placebo. At 48 hours in the abdominoplasty study, the mean pain score was about 4.0 with suzetrigine and 5.3 with placebo.

Adverse reactions and concerns

In the clinical trials, the most common adverse reactions (greater incidence in participants in the suzetrigine group as compared with the placebo group) were pruritus (itching), muscle spasms, increased blood levels of creatine phosphokinase (a muscle enzyme that is a biomarker for tissue degradation), and rash.[7] Pruritus was the most frequent adverse effect, occurring in 2.1% of participants who used suzetrigine for 48 hours, compared with 1.6% of participants in the placebo group.

Increased creatine phosphokinase levels occurred in 1.1% of participants in the suzetrigine group and 0.5% of those in the placebo group.[8] The FDA reviewer downplayed the significance of the elevated enzyme levels, noting that they did not coincide with concerning signs or symptoms and that their magnitudes were “relatively small and unlikely to be clinically significant.”

Because of concerns about the potential effects of suzetrigine on pregnancy and lactation, the FDA is requiring two post-marketing studies. A pregnancy outcome study is to be completed by 2036. The study will use electronic health records and other medical data to assess spontaneous miscarriages, stillbirths, neonatal deaths, major congenital malformations, and preterm and low-birth-weight births in persons exposed to suzetrigine during pregnancy. A lactation outcome study to be completed by 2028 will assess infants exposed to suzetrigine and measure the drug’s concentration in breast milk.

FDA reviewers noted that female rats administered high doses (2.2 times the recommended human dose) of suzetrigine just prior to mating and through gestation day seven were more likely to have preimplantation loss, which is the failure of a fertilized egg to implant in the uterus and develop into a pregnancy.

What You Can Do

Suzetrigine is a new drug that has only been compared with hydrocodone/acetaminophen and placebo in clinical trials. These short-term studies showed that suzetrigine has small benefits over placebo. Head-to-head comparisons of suzetrigine with ibuprofen, acetaminophen and other non-opioid analgesic drugs are needed, as are comparisons to nonpharmacologic methods for pain relief. Moreover, the longer-term (beyond 48 hours) adverse effects of suzetrigine use have not been elucidated, and its use for the treatment of acute pain has not been studied beyond 14 days.

For these reasons, Public Citizen’s Health Research Group has classified suzetrigine as Do Not Use for Seven Years. This is our usual classification for new drugs that do not represent clinical breakthroughs.

If you are experiencing acute pain, you should first consider nonpharmacologic approaches (for example, ice and elevation) and medications that are available without a prescription, such as ibuprofen and other nonsteroidal anti-inflammatory drugs. For severe pain following surgery or physical trauma, discuss with your clinician the potential role for short-term use of prescription pain medications, such as opioids.
 

References

[1] Mariano ER. Approach to the management of acute pain in adults. UpToDate. April 14, 2025.

[2] Williamson KJ, Stram ML. The epidemiology of inadequate control of acute pain. In: Abd-Elsayed A (eds). Pain. Springer, Cham; 2019:1005–1007.

[3] Mariano ER. Approach to the management of acute pain in adults. UpToDate. April 14, 2025.

[4] Food and Drug Administration. FDA news release. FDA approves novel non-opioid treatment for moderate to severe acute pain. January 30, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-novel-non-opioid-treatment-moderate-severe-acute-pain. Accessed May 5, 2025.

[5] Suzetrigine (Journavx) - a sodium channel blocker for acute pain. Med Lett Drugs Ther. 2025.67(1723):33-35.

[6] Food and Drug Administration. Center for Drug Evaluation and Research. Application Number: 219209Orig1s000. Integrated review. Suzetrigine. January 30, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2025/219209Orig1s000IntegratedR.pdf. Accessed May 5, 2025.

[7] Vertex Pharmaceuticals Incorporated. Label: suzetrigine (JOURNAVX). January 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/219209Orig1s000lbl.pdf. Accessed May 5, 2025.

[8] Aujla RS, Zubair M, Patel R. Creatine phosphokinase. February 27, 2024. In: StatPearls. Treasure Island (FL).