in pictures and a few words
What it is and why it matters
This is a new medicine for severe pain. It is not an opioid and works in a new way — nothing like it has appeared for decades.
- It is prescribed to adults for severe acute pain, including after surgery
- It was approved in the US in early 2025
- It is a prescription-only medicine
How it works
Pain travels along a nerve like a signal along a wire. The medicine switches off a special channel in the nerve, and the signal does not reach the brain.
- The signal is switched off where it starts
- The medicine does not act in the brain
A third way against pain
Until now pain was eased in two ways: with anti-inflammatory medicines and with opioids, which act in the brain. This medicine takes a third way.
- Anti-inflammatories: limited strength and a cost to the stomach and kidneys
- Opioids: drowsiness, needing more over time, and addiction
- The new medicine switches off the signal in the nerve, not in the brain
It helps after surgery
The medicine was tested in people after operations that usually hurt a lot: on the belly and on the foot. They were followed for the first two days.
- In both cases pain eased better than on a dummy pill
- Relief came sooner than on a dummy pill
- It was also compared with an opioid: it was not stronger, no difference was found
Tested in people. Tested in people: in two large studies after surgery, pain eased better than on a dummy pill.
What about addiction?
The medicine does not act in the brain. So scientists expect that people will not get hooked on it or addicted.
- This is an expectation based on how the medicine is built
- Studies have not yet measured addiction: they lasted only two days
How to take it
This is a medicine for a few days of acute pain, not for taking all the time.
- Tablets are swallowed whole
- The first dose on an empty stomach: an hour before food or two hours after
- It cannot be bought in Europe or Ukraine: it is sold on prescription in the US
What can happen while taking it
More often than on a dummy pill there was itching, rash, muscle spasms and a rise in one muscle marker in a blood test.
- At twice the usual blood level, no dangerous lengthening of an interval on the ECG
What comes next
The medicine is now being tested for long-lasting nerve pain — for example, in diabetes.
- If the benefit is confirmed, it will become another option for long-lasting nerve pain
- It has not yet been studied in endometriosis
Who should see a doctor first
This medicine is prescription-only. Tell your doctor about all the medicines you take.
- Some medicines must not be combined with it; avoid grapefruit for the whole course
- Liver disease or pregnancy — see a doctor first; safety in children is not established
- With some hormonal contraceptives — non-hormonal protection during use and 28 days after
Important. If it is offered to you for long-lasting, chronic pain, that is outside the label — and the conversation with your doctor should start right there.
In one sentence
The new medicine switches off pain right in the nerve, not in the brain: after surgery it eased pain better than a dummy pill, and it is taken for a few days on prescription.
Key points
Suzetrigine (Journavx) is the first painkiller of a new class in decades: it blocks the NaV1.8 sodium channel in peripheral nerves, and the pain signal does not reach the brain.
| Situation | How it helps | What human studies showed |
|---|---|---|
| Moderate to severe acute pain in adults | the main indication: approved by the FDA on 30 January 2025 as a new molecular entity; since January 2026 the label names postoperative pain explicitly | two phase 3 trials: significantly better than placebo in both (Bertoch T, Anesthesiology 2025) |
| Pain after abdominoplasty | relieves pain in the first 48 hours after surgery | 1,118 participants: pain relief versus placebo 48.4 (CI 33.6–63.1), p < 0.0001; meaningful relief at 119 min vs 480 on placebo |
| Pain after bunion surgery on the foot | relieves pain in the first 48 hours after surgery | 1,073 participants: pain relief versus placebo 29.3 (CI 14.0–44.6), p = 0.0002; meaningful relief at 240 min vs 480 |
| Painful diabetic neuropathy | under study: three phase 3 trials are running, one phase 2 trial is complete | — |
| Painful lumbosacral radiculopathy, small fibre disease | under study: there are research programmes | — |
How it helps
For decades pain relief has rested on two pillars: non-steroidal anti-inflammatories, which suppress inflammation, and opioids, which act in the brain. The first have a ceiling of effect and their own price for stomach and kidneys; the second bring sedation, tolerance and dependence — the dependence that cost the United States an epidemic.
Suzetrigine is built differently. It selectively blocks the NaV1.8 sodium channel — that one out of the nine known voltage-gated sodium channels. The channel operates in peripheral sensory neurons, including dorsal root ganglion neurons, and transmits pain signals. The label describes the result this way: by inhibiting NaV1.8, the drug inhibits transmission of pain signals to the spinal cord and brain. The signal is damped where it arises, not where it is perceived.
Hence the central promise: relief without reinforcement, and therefore without addiction. This is an expectation from the mechanism, and a logical one: the drug does not act in the brain, so it has nothing to reinforce behaviour with.
What the trials showed
Approval rested on two phase 3 trials, published together (Bertoch T, Anesthesiology 2025). Both models are elective surgery with predictably severe pain afterwards: NAVIGATE 2, abdominoplasty, and NAVIGATE 1, bunion surgery on the foot.
Follow-up ran 48 hours. The comparison was against two things at once: placebo, and a live competitor — the hydrocodone/acetaminophen combination, that is, an opioid.
The headline result: the drug works, and against placebo that is shown convincingly in both operations (the figures are in the table above). The authors describe pain reduction with suzetrigine as «similar» to the opioid combination.
What comes next
Chronic pain is already being studied, and this is the most interesting direction. In painful diabetic neuropathy three phase 3 trials are running and one phase 2 trial is complete. There are programmes in painful lumbosacral radiculopathy and in small fibre disease.
If the effect holds up in chronic neuropathic pain, the drug's significance changes in kind: today it is an alternative to an opioid for a few days after surgery; there it would be an alternative to gabapentinoids and antidepressants for months.
How to take it
Tablets are swallowed whole; the starting dose is taken on an empty stomach, an hour before food or two hours after, otherwise onset is delayed.
- This is medicine for days, not for continuous use. All available efficacy data were gathered over 48 hours.
- Where it is sold. The drug is prescription-only and sold in the US; no registration could be found in the European Union, the United Kingdom or Ukraine.
Who should see a doctor first
This is a prescription drug, and its warnings section is not a formality.
- One contraindication, and it matters: strong CYP3A inhibitors. Concomitant use is prohibited because they raise exposure to the drug and its active metabolite.
- Avoid grapefruit throughout treatment, for the same reason.
- Liver. In severe hepatic impairment (Child-Pugh class C) use should be avoided; in moderate impairment (class B) the dose is lower.
- Hormonal contraception. The drug is itself a CYP3A inducer. If the contraceptive contains a progestin other than levonorgestrel or norethindrone, an additional non-hormonal method is needed during treatment and for 28 days after it.
- Common adverse reactions, more frequent than on placebo: pruritus, muscle spasms, raised creatine phosphokinase, rash.
- Pregnancy. There are no data on use in pregnancy. In rat studies, effects on implantation and maintenance of pregnancy occurred at doses from 2.2 times the maximum recommended human dose.
- The indication is limited to acute pain in adults. Safety and effectiveness have not been established in children.
- If it is offered to you for chronic pain, that is off-label prescribing, and the conversation with your doctor should start there.
On the heart, separately: at twice the exposure of the maximum recommended dose, no clinically significant QT prolongation was observed.
Bottom line
Suzetrigine is a genuine event in pain pharmacology: for the first time in decades pain relief has taken a fundamentally different route — not through the brain, but by switching off the signal in the nerve itself. Against placebo the drug works; that is shown in two phase 3 trials.
That route has a chance of delivering what opioids cannot — relief that does not reinforce itself. And studies in chronic pain are already under way.
Caveats
- Versus the opioid. Superiority over hydrocodone/acetaminophen was not shown. This was not an incidental finding but a pre-planned test — the first of the key secondary endpoints. Verbatim: «Neither trial achieved the first key secondary endpoint of superiority of suzetrigine versus hydrocodone bitartrate/acetaminophen on SPID48». «Similar» does not mean «weaker than opioids» — no difference was found — but nor does it mean «proven to be no worse»: an absence of statistical difference does not by itself establish equivalence, which requires a different trial design and a pre-specified margin.
- Methodological critique (Mistry T, Saudi J Anaesth 2026): «Absence of statistical difference in the setting of marked heterogeneity and wide confidence intervals does not establish therapeutic equivalence». The same letter raises two objections to the pooled analysis of the drug's data: extremely high heterogeneity between the included studies, and the fact that only the highest-dose arms were pooled, which inflates the effect estimate.
- Spread between operations. 48.4 and 29.3 — a near-twofold difference: the size of the effect depends markedly on which surgery it was, and the figure cannot be carried from one situation to another.
- Speed of relief. 119 versus 480 minutes is the result from one of the two operations; after foot surgery it was 240 versus 480 — twice as fast, not four times. The authors mark both estimates as descriptive: in this design the endpoints are tested in sequence, and since superiority over the opioid was not met, everything after it loses confirmatory status. Formally this is an observation, not a proven result.
- Addiction. The phrase about relief «without addiction concerns» sits in the paper's background section, among descriptions of the potential the mechanism offers — it is a hypothesis. The trials themselves did not measure addiction: neither tolerance nor abuse potential were endpoints, and 48 hours of follow-up is unsuited to that question in principle. No separate abuse-potential study could be found in the publication database. The mechanism gives grounds to expect; the data that would show it do not exist.
- Who paid for the research. Five authors of the pivotal publication are employees of the manufacturer, holding its stock and options; eight more received company fees as members of its acute pain steering committee; one author declared no conflict of interest. Such a structure is typical of pivotal trials, but that is exactly why independent critique and subsequent comparisons carry more weight than usual.
- Chronic pain. Trials are running; there are no results yet.
- Endometriosis. There are no clinical data at all: not a single registered trial of suzetrigine in endometriosis, pelvic pain or dysmenorrhoea — verified both in the publication database, through ten different query formulations, and in the trials registry, where the drug has 48 studies and none on this topic. The target has been studied only in the laboratory, on endometrioma tissue and cell lines, without the drug itself (Zhu TH, Reproduction 2018). The only trial that mentions the pelvis at all is pain relief after pelvic floor surgery, and its criteria list chronic pain syndromes among the exclusions. There are grounds for scientific interest, and no grounds for a patient's expectations.
- Chronic pelvic pain is not the same as endometriosis: it has other causes that are treated differently — pelvic congestion syndrome, for one.
This material is for information only and does not replace a consultation with a doctor. Suzetrigine is a prescription drug: the decision to take it rests with the doctor.
References
- Bertoch T, Anesthesiology 2025. PMID 40117446
- Mistry T, Saudi J Anaesth 2026. PMID 42553835
- Zhu TH, Reproduction 2018. PMID 29074615
Key facts
- Approved by the FDA on 30 January 2025 as a new molecular entity — the first painkiller of a new class in decades; the indication is moderate to severe acute pain in adults, with postoperative pain named explicitly in the label since January 2026.
- It selectively blocks the NaV1.8 sodium channel in peripheral sensory neurons and inhibits transmission of pain signals to the spinal cord and brain: the signal is damped where it arises, not where it is perceived.
- Two phase 3 trials, 1,118 and 1,073 participants: the drug significantly beat placebo in both — after abdominoplasty and after foot surgery.
- Chronic pain is already being studied: in painful diabetic neuropathy three phase 3 trials are running and one phase 2 trial is complete.
- Contraindicated with strong CYP3A inhibitors; not for use in severe hepatic impairment, and progestin-based hormonal contraception requires an additional non-hormonal method.
