Suzetrigine in acute pain: non-opioid analgesic and dose

A 45-year-old woman is going to have bunion surgery, a bunionectomy, on her right foot. Six years ago she had opioid use disorder after a long treatment for back pain, and she is in remission, followed with buprenorphine. She is afraid of pain after surgery and even more afraid of using opioids again. She also uses an oral contraceptive and drinks grapefruit juice at breakfast. She asks whether there is a strong pain medicine that is not an opioid. The scene is fictional and was written for teaching.

This text uses the case as a clinical reasoning scenario for students and health professionals. It covers suzetrigine, a selective blocker of the NaV1.8 sodium channel, approved in the United States for moderate to severe acute pain in adults. The text explains the indication, the dose, the interactions, the effect on contraceptives, what the studies showed and where the limits of the evidence are. It does not replace your institution's analgesia protocol or the local package insert. If you play the case of the day on NEXO, you will recognize the challenge: deciding with clues that arrive in sequence.

Key points

• Suzetrigine (brand name Journavx) is indicated in the United States for moderate to severe acute pain in adults and has not been studied for more than 14 days.
• The dose is 100 mg on an empty stomach, followed by 50 mg every 12 hours, starting 12 hours after the first dose.
• It is contraindicated with strong CYP3A inhibitors; moderate inhibitors and moderate hepatic impairment require a reduced regimen, and foods with grapefruit should be avoided.
• It may reduce the effect of contraceptives with progestogens other than levonorgestrel or norethisterone; in that case, the package insert calls for an additional non-hormonal method until 28 days after stopping.
• In phase 3 studies, it was superior to placebo after abdominoplasty and bunionectomy, but it did not beat hydrocodone with paracetamol in either of the two.
• The regulatory dates in this text were checked with the FDA and the EMA on October 24, 2026.

Why this is a reasoning scenario

Pain after surgery is expected, and treating it well is part of care. For someone who has had opioid use disorder, every opioid prescription carries an extra risk of relapse. An analgesic from another class, one that acts on peripheral nerves and not on the brain, seems like the ideal answer. But the real answer is more complex: the new medicine has a modest average effect, important interactions and little experience outside the studies.

The scenario is good for training because it forces you to weigh benefit, risk and context. You need to know the surgery and the expected pain, the history of opioid use, the buprenorphine, the liver and the kidneys, the medicines in use, the contraceptive and even the breakfast. The post on signs, symptoms and history helps organize this collection, and the post on clinical decision making reminds you that choosing an analgesic is a decision with a trade-off of risks.

What the scene teaches

The scene trains six habits. The first is planning analgesia before surgery, together with the team. The second is not stopping buprenorphine on your own. The third is knowing the place of suzetrigine within multimodal analgesia. The fourth is reviewing CYP3A interactions, including with foods. The fifth is remembering the contraceptive. The sixth is agreeing on what to do if the pain does not improve.

What is not at stake

The text does not discuss chronic pain, neuropathic pain or use of suzetrigine for more than two weeks, which are outside the American indication. It also does not compare prices. The post on diagnostic uncertainty helps explain to the patient what is not yet known about a recent medicine.

Acute pain and the opioid problem

The 2022 CDC guideline on opioid prescribing defines acute pain as pain lasting less than one month, usually caused by injury, trauma or procedures such as surgery (Dowell et al., 2022). The first recommendation of the guideline says that non-opioid therapies are at least as effective as opioids for many common types of acute pain (Dowell et al., 2022). The guideline also notes that unresolved acute pain can progress to chronic pain (Dowell et al., 2022).

Why a new painkiller drew attention

A review on suzetrigine describes the context of the opioid crisis in the United States and calls the drug the first non-opioid painkiller approved in more than two decades (Pham et al., 2025). A review on emergency use notes that American emergency departments receive more than 140 million visits per year, and that pain is one of the most common complaints (Bradshaw et al., 2026). Interest is high, but the enthusiasm must be measured against the study numbers.

The patient in recovery

A narrative review on buprenorphine in the perioperative period summarizes two main conclusions of a consensus: buprenorphine should not be routinely stopped in the perioperative period, to reduce the risk of relapse, and it can be started in people with untreated disorder and acute pain (Kohan et al., 2025). The same review says that multimodal analgesia and regional or local anesthesia techniques are essential (Kohan et al., 2025). For the patient in the scene, suzetrigine may be one more piece of that plan, not a substitute for it.

Applying it to the patient

Bunionectomy is a classic model of moderate to severe acute pain in painkiller studies. The patient has a strong reason to avoid opioids, and buprenorphine should continue. The plan can combine a regional block, paracetamol, an anti-inflammatory when permitted, ice and a raised foot, with suzetrigine as a non-opioid oral option. The post on interprofessional clinical reasoning shows how anesthesia, surgery, pharmacy and nursing put this plan together.

How suzetrigine works

The American label describes suzetrigine as a selective blocker of the voltage-gated sodium channel NaV1.8, compared with the other known channels, NaV1.1 through NaV1.9 (American label for Journavx, 1/2026). NaV1.8 is in peripheral sensory neurons, including those of the dorsal root ganglion, where it helps transmit pain signals (American label for Journavx, 1/2026). By blocking this channel, the drug reduces the signal reaching the spinal cord and the brain (American label for Journavx, 1/2026).

The active metabolite

The main active metabolite, called M6-SUZ, is about 3.7 times less potent than suzetrigine on NaV1.8 (American label for Journavx, 1/2026). Both are metabolized by CYP3A, and that explains the list of interactions (American label for Journavx, 1/2026).

No central effect

A pharmacology study describes suzetrigine as a potent and highly selective inhibitor of NaV1.8 (Osteen et al., 2025). The authors report no adverse effects on the central nervous system, the cardiovascular system or behavior, and no evidence of dependence potential in the studies performed (Osteen et al., 2025). The American label shows no clinically significant effect on the QTc interval at twice the exposure of the maximum dose (American label for Journavx, 1/2026). A clinical pharmacology review summarizes these data and the translation of the mechanism to the clinic (Rajasingham and Qi, 2025).

What is still unknown

Reviews point out that the mechanism may also play a role in neuropathic pain, but this is still a research hypothesis (Mach et al., 2025). Another review notes that the lack of long-term safety data limits use to courses of up to 14 days and cites concern about cost (Jones et al., 2025). The post on differential diagnosis helps remind us that pain that does not improve may have another cause, such as infection or thrombosis.

Regulatory situation: FDA and EMA

United States. The FDA approved Journavx on January 30, 2025, under NDA 219209, as a new molecular entity, with priority review (Drugs@FDA, NDA 219209). The most recent supplement listed in Drugs@FDA is dated January 23, 2026, a text change to the label and the patient leaflet (Drugs@FDA, NDA 219209). The label consulted was revised in January 2026 (US Journavx label, 1/2026). The indication is the treatment of moderate to severe acute pain in adults (US Journavx label, 1/2026).

European Union. On October 24, 2026, we did not find an authorized medicine page for suzetrigine on the EMA website. Therefore, this text does not describe the European regulatory situation.

Other countries. This text does not describe registration in other countries. Availability depends on the local agency.

What the studies showed

Two phase 3 studies, randomized, double-blind and controlled by placebo and by hydrocodone with acetaminophen, supported the approval (Bertoch et al., 2025). The primary endpoint was the time-weighted sum of the pain intensity difference from 0 to 48 hours, called SPID48, compared with placebo (Bertoch et al., 2025). The higher the value, the greater the pain reduction (Bertoch et al., 2025). In both studies, rescue ibuprofen was allowed (Bertoch et al., 2025).

Abdominoplasty

In the study after abdominoplasty, with 1118 participants, 447 received suzetrigine (US Journavx label, 1/2026). The mean SPID48 was 118.4 with suzetrigine, 70.1 with placebo and 111.8 with hydrocodone and acetaminophen (US Journavx label, 1/2026). The difference compared with placebo was 48.4 points, and the difference compared with hydrocodone with acetaminophen was 6.6 points, with a confidence interval that includes zero (US Journavx label, 1/2026).

Bunionectomy

In the study after bunionectomy, with 1073 participants and a mean age of 48 years, 426 received suzetrigine (US Journavx label, 1/2026). The mean SPID48 was 99.9 with suzetrigine, 70.6 with placebo and 120.1 with hydrocodone and acetaminophen (US Journavx label, 1/2026). The difference compared with placebo was 29.3 points; compared with hydrocodone with acetaminophen, it was minus 20.2 points, that is, the opioid relieved pain more in this study (US Journavx label, 1/2026).

The table summarizes the two studies, according to the US label.

Study	SPID48 with suzetrigine	SPID48 with placebo	SPID48 with hydrocodone and acetaminophen	Difference against placebo	Source
Abdominoplasty	118.4	70.1	111.8	48.4	(US Journavx label, 1/2026)
Bunionectomy	99.9	70.6	120.1	29.3	(US Journavx label, 1/2026)

Time to relief

The median time to a drop of at least 2 points on the pain scale was 119 minutes with suzetrigine and 480 minutes with placebo after abdominoplasty, and 240 versus 480 minutes after bunionectomy (Bertoch et al., 2025). For the patient in the scene, this means that relief may take a few hours, and the plan needs to cover that interval.

Outside the two main studies

In a single-arm phase 3 study, with 256 participants with acute surgical or non-surgical pain, 83.2 percent rated the effect as good, very good or excellent at the end of treatment (McCoun et al., 2025). In this study, rescue acetaminophen and ibuprofen were allowed (McCoun et al., 2025). A meta-analysis of randomized studies against placebo found a mean pain reduction of 0.66 points at 24 and 48 hours, with high heterogeneity (Alvarez-Aguilar and Picado-Loaiza, 2026). The same meta-analysis showed a lower risk of nausea and dizziness with suzetrigine than with placebo (Alvarez-Aguilar and Picado-Loaiza, 2026).

Adverse events

In the American prescribing information, the adverse reactions reported more often than with placebo were itching, in 2.1 versus 1.6 percent, muscle spasms, in 1.3 versus 0.5 percent, increased creatine phosphokinase, in 1.1 versus 0.5 percent, and skin spots, in 1.1 versus 0.5 percent (American prescribing information for Journavx, 1/2026). In the abdominoplasty study, nausea or vomiting occurred in 20 percent with suzetrigine, 33 percent with hydrocodone and acetaminophen and 25 percent with placebo (American prescribing information for Journavx, 1/2026). Only 6.3 percent of patients in the phase 3 studies were 65 or older (American prescribing information for Journavx, 1/2026).

How to read these numbers

The SPID48 adds up, over 48 hours, how much the pain dropped compared with the start, giving weight to time. It is useful for comparing groups, but it does not say how much relief a person will feel. A difference of 29 points over 48 hours, as in the bunionectomy, amounts to a small average improvement at each moment, and the meta-analysis found a difference of less than one point on the 0 to 10 pain scale (Alvarez-Aguilar and Picado-Loaiza, 2026). In other words, the drug works better than placebo, but the average effect is modest, and many patients in the studies used rescue ibuprofen (Bertoch and colleagues, 2025).

It is also worth noting who was left out. The main studies were done in adults healthy enough for elective surgery, with few older people (American prescribing information for Journavx, 1/2026). A review for emergency medicine recalls that the drug was not studied in people with a glomerular filtration rate below 15 mL/min or for more than 14 days (Bradshaw and colleagues, 2026). For the patient in the scene, the history of opioid use disorder was also not the focus of these studies, and so the plan needs close follow-up.

From the first dose to discharge

Before prescribing, three questions change the approach: which medicines the patient uses, how her liver is doing and which contraceptive she uses.

The dose

The American prescribing information calls for 100 mg as the first dose, on an empty stomach, at least 1 hour before or 2 hours after eating (American prescribing information for Journavx, 1/2026). Twelve hours later, 50 mg every 12 hours begins, which can be taken with or without food (American prescribing information for Journavx, 1/2026). Use has not been studied for more than 14 days (American prescribing information for Journavx, 1/2026). If the patient forgets a dose, she should take it as soon as she remembers; if she forgets two or more, she should take 100 mg and resume the schedule (American prescribing information for Journavx, 1/2026).

Interactions and grapefruit juice

Suzetrigine is contraindicated with strong CYP3A inhibitors (American prescribing information for Journavx, 1/2026). With moderate inhibitors, the prescribing information calls for 100 mg as the first dose, 50 mg every 12 hours for doses 2 to 4 and then 50 mg every 24 hours (American prescribing information for Journavx, 1/2026). Strong and moderate CYP3A inducers should be avoided, because they reduce the effect (American prescribing information for Journavx, 1/2026). Foods and drinks with grapefruit should also be avoided during use (American prescribing information for Journavx, 1/2026). The patient needs to swap her breakfast juice for another one.

The contraceptive

If the contraceptive has a progestogen other than levonorgestrel or norethisterone, the prescribing information calls for an additional non-hormonal method, such as a condom, or another contraceptive, during use and for 28 days after stopping (American prescribing information for Journavx, 1/2026). Combinations of ethinylestradiol with levonorgestrel or norethisterone and the intrauterine system are alternatives cited in the prescribing information (American prescribing information for Journavx, 1/2026).

Liver and kidneys

In moderate hepatic impairment, Child-Pugh B, the prescribing information calls for the same reduced schedule used with moderate inhibitors (American prescribing information for Journavx, 1/2026). In severe hepatic impairment, Child-Pugh C, and with a glomerular filtration rate below 15 mL/min, use should be avoided (American prescribing information for Journavx, 1/2026). Pregnancy has no human data, and studies in rats showed effects on implantation and maintenance of pregnancy at doses above the maximum human dose (American prescribing information for Journavx, 1/2026).

• First dose of 100 mg on an empty stomach; then 50 mg every 12 hours.
• Do not use with strong CYP3A inhibitors; reduced schedule with moderate inhibitors or Child-Pugh B.
• Avoid strong and moderate CYP3A inducers and foods with grapefruit.
• Additional non-hormonal method if the progestogen is not levonorgestrel or norethisterone, for up to 28 days afterwards.
• Avoid in Child-Pugh C and with glomerular filtration below 15 mL/min.
• Do not use for more than 14 days, because it has not been studied beyond that.

Source of the list: (US label for Journavx, 1/2026).

Applying it to the patient

The patient stays on buprenorphine, as per the perioperative review (Kohan et al., 2025). The team plans a regional block and multimodal analgesia, and considers suzetrigine as a non-opioid oral option. First, the pharmacy checks whether any medicine in use inhibits or induces CYP3A and which progestogen the contraceptive contains. The patient is advised to avoid grapefruit and to report if the pain does not improve, because in the bunionectomy study the opioid relieved pain more on average (US label for Journavx, 1/2026). The post about diagnostic pause reminds you to review the plan if the pain departs from what is expected.

How NEXO helps train this reasoning

In NEXO, the case of the day is fictional, with a real clinical presentation and up to six progressive clues, and you propose the diagnosis by looking for the ICD-10 code. Pain after surgery is a good exercise because a contraceptive, an antifungal or a juice changes the approach. The post about case-based learning explains why this format fixes knowledge.

Three exercises with cases

Change the medicines. Say what to do if the patient were taking an antifungal that strongly inhibits CYP3A.

Change the liver. Say how to adjust the dose if she had Child-Pugh B cirrhosis.

Change the course. Say what to investigate if the pain worsened on the third day, with a warm, swollen foot.

The post about simulation of a consultation helps train the conversation about pain expectations.

The limits on using the game are described on the NEXO economy page. If you research teaching of clinical reasoning, the page for researchers explains how to get in touch. Professionals who write or review cases find information on curation and on creators, and institutions can learn about the proposal on the partnerships page.

Frequently asked questions

Is suzetrigine an opioid?

No. It blocks the NaV1.8 sodium channel in peripheral sensory nerves (US label for Journavx, 1/2026).

Does it relieve pain as much as an opioid?

In phase 3 studies, it did not beat hydrocodone with paracetamol, and in the bunionectomy study the opioid was better on average (US label for Journavx, 1/2026).

What is the dose?

100 mg on an empty stomach for the first dose and then 50 mg every 12 hours, for up to 14 days (US label for Journavx, 1/2026).

Can I take it with grapefruit juice?

No. The label asks you to avoid foods and drinks with grapefruit (US label for Journavx, 1/2026).

Does it interfere with the contraceptive?

It may interfere with those that have progestogens other than levonorgestrel or norethisterone; in that case, use an additional method for up to 28 days afterwards (US label for Journavx, 1/2026).

Final checklist

• I planned the analgesia before surgery, with the team.
• I kept the buprenorphine and agreed the plan with the person who prescribes it.
• I reviewed the medicines in use for CYP3A inhibitors and inducers.
• I asked about the contraceptive and the progestogen.
• I advised avoiding grapefruit.
• I checked the liver and the kidneys.
• I explained the starting dose on an empty stomach and the 14-day limit.
• I agreed what to do if the pain does not improve.

Want to practice reasoning with progressive clues? Play the case of the day.

References

1. Alvarez-Aguilar P, Picado-Loaiza S. Suzetrigine (a NaV1.8 inhibitor) versus placebo for acute postoperative pain: A systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore). 2026. PMID 41790692.
2. 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. PMID 40117446.
3. Bradshaw JC, Lester L, Leon DA. Suzetrigine for Acute Pain in the Emergency Department: A First-in-Class NaV1.8 Blocker. J Am Coll Emerg Physicians Open. 2026. PMID 41767204.
4. Dowell D, Ragan KR, Jones CM, et al. CDC Clinical Practice Guideline for Prescribing Opioids for Pain - United States, 2022. MMWR Recomm Rep. 2022. PMID 36327391.
5. Jones M, Demery A, Al-Horani RA. Suzetrigine: A Novel Non-Opioid Analgesic for Acute Pain Management-A Review. Drugs Drug Candidates. 2025. PMID 40799996.
6. Kohan L, Barreveld A, Potru S, et al. Narrative review: Managing buprenorphine and opioid use disorder in the perioperative setting. Pain Pract. 2025. PMID 39450825.
7. Mach M, Giba A, Miedziaszczyk M, et al. Suzetrigine as a Novel Non-opioid Analgesic Drug in Pain Management: A Review of Clinical Evidence and Therapeutic Perspectives. Cureus. 2025. PMID 40862032.
8. McCoun J, Winkle P, Solanki D, et al. Suzetrigine, a Non-Opioid Na(V)1.8 Inhibitor With Broad Applicability for Moderate-to-Severe Acute Pain: A Phase 3 Single-Arm Study for Surgical or Non-Surgical Acute Pain. J Pain Res. 2025. PMID 40165940.
9. Osteen JD, Immani S, Tapley TL, et al. Pharmacology and Mechanism of Action of Suzetrigine, a Potent and Selective Na(V)1.8 Pain Signal Inhibitor for the Treatment of Moderate to Severe Pain. Pain Ther. 2025. PMID 39775738.
10. Pham A, Yep H, Wozniak S, et al. Beyond Opioids: A Review of Suzetrigine for Acute Pain Management. Int J Mol Sci. 2025. PMID 41155158.
11. Rajasingham R, Qi Y. Suzetrigine, a Non-Opioid Small-Molecule Analgesic: Mechanism of Action, Clinical, and Translational Science. Clin Transl Sci. 2025. PMID 41251403.
12. U.S. Food and Drug Administration. Drugs@FDA: FDA-Approved Drugs. NDA 219209, Journavx. Accessed on 10/24/2026. Official source.
13. Vertex Pharmaceuticals. JOURNAVX (suzetrigine) tablets, for oral use. Prescribing Information. Revised in 1/2026. Accessed on 10/24/2026. Official source.