Explore the Clinical Data for JOURNAVX® (suzetrigine)

JOURNAVX is an oral nonopioid indicated for the treatment of moderate-to-severe acute pain in adults—the first and only oral pain signal inhibitor highly selective for Na_V1.8^1,2

• By inhibiting Na_V1.8, JOURNAVX blocks sodium ions from entering pain-sensing neurons, disrupting the initiation and propagation of action potentials and reducing pain signal transmission from the PNS to the CNS^1,2
• Because JOURNAVX is a highly selective inhibitor of Na_V1.8 (≥31,000x more selective of Na_V1.8 than all other Na_V subtypes as measured in vitro), it inhibits pain signal transmission to the spinal cord and brain^1,2
• JOURNAVX does not interact with μ receptors, which are associated with addiction^2,3
• There is no evidence that JOURNAVX has addictive potential based on available data, including the MOA of JOURNAVX, preclinical data, and clinical adverse event data²
• JOURNAVX is not a controlled substance⁴

Study design and endpoints

• The efficacy of JOURNAVX in the treatment of moderate-to-severe acute pain in adults was established in 2 randomized, double-blind, placebo- and hydrocodone bitartrate/acetaminophen (HB/APAP)–controlled trials of acute pain, one following full abdominoplasty and the other following bunionectomy¹
• Patients were randomized to receive JOURNAVX (initial dose of 100 mg followed by 50 mg every 12 hours), HB/APAP (5 mg/325 mg every 6 hours), or placebo for a duration of 48 hours. The full abdominoplasty study enrolled 1118 patients; of these patients, 447 received JOURNAVX, 448 received HB/APAP, and 223 received placebo. The bunionectomy study enrolled 1073 patients; of these patients, 426 received JOURNAVX, 431 received HB/APAP, and 216 received placebo. Patients were evaluated from 0 to 48 hours^1,a
• The studies measured efficacy utilizing the time-weighted sum of the pain intensity difference (SPID) from 0 to 48 hours (SPID48). SPID48 was calculated using patient-reported scores on the Numeric Pain Rating Scale (NPRS) over the 48-hour treatment period. Higher SPID values represent greater reductions in pain^1,5
• The primary endpoint tested JOURNAVX superiority vs placebo on SPID48^1,6
• A key secondary endpoint tested JOURNAVX superiority vs HB/APAP on SPID48^1,6

JOURNAVX met the primary endpoint by demonstrating statistically significant superior reduction in pain vs placebo.^1,b

JOURNAVX did not meet the first key secondary endpoint that hypothesized superior reduction in pain vs HB/APAP.^1,6

SPID48 results^1,6

Mean pain intensity over time¹

Pre-rescue pain scores were carried forward for 6 hours following the use of rescue medication.¹

The NPRS vs time analysis was not a prespecified study objective. It is not intended to convey a measure of efficacy.

JOURNAVX was generally well tolerated across all Phase 3 pivotal trials¹

JOURNAVX safety data were collected from 2 pooled, double-blind, placebo- and HB/APAP–controlled trials that enrolled 874 patients with moderate-to-severe acute pain following full abdominoplasty (Trial 1) and bunionectomy (Trial 2).¹

• Adverse reactions reported in ≥1% of patients treated with JOURNAVX and greater than rate of placebo in pivotal trials were pruritus, muscle spasms, increased blood creatine phosphokinase, and rash¹
• No adverse reactions occurred in patients treated with JOURNAVX at a frequency higher than placebo by ≥1%¹
• Discontinuation due to adverse events in Trials 1 and 2 was 0.6% in the JOURNAVX group, 0.2% in the placebo group, and 0.6% in the HB/APAP group¹

Learn more about JOURNAVX

^a 400 mg of ibuprofen every 6 hours, as needed for pain relief, was permitted as a rescue medication across all treatment groups.¹

^b As measured by the time-weighted sum of the pain intensity difference (SPID) as recorded on the Numeric Pain Rating Scale (NPRS) from 0 to 48 hours (SPID48).

^c A larger value of LS mean indicates better efficacy measured by SPID48.

CI, confidence interval; CNS, central nervous system; LS, least squares; MOA, mechanism of action; Na_V, voltage-gated sodium channel; PNS, peripheral nervous system; q6h, every 6 hours; q12h, every 12 hours; SE, standard error.

INDICATION AND IMPORTANT SAFETY INFORMATION

INDICATION

JOURNAVX is indicated for the treatment of moderate-to-severe acute pain in adults.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

Concomitant use of JOURNAVX with strong CYP3A inhibitors is contraindicated.

WARNINGS AND PRECAUTIONS

Increased Risk of Adverse Reactions With Concomitant Use With Strong and Moderate CYP3A Inhibitors: Strong and moderate CYP3A inhibitors increase suzetrigine and its active metabolite exposures, which may cause adverse reactions with JOURNAVX.

Risk of Drug Interactions With Certain CYP3A Substrates: Suzetrigine is an inducer of CYP3A. If JOURNAVX is used concomitantly with sensitive CYP3A substrates or CYP3A substrates where minimal concentration changes may lead to loss of efficacy, refer to the Prescribing Information for the CYP3A substrates for dosing instructions. Dosage adjustment of the concomitant CYP3A substrates may be required when initiating or discontinuing JOURNAVX.

Risk of Drug Interactions With Certain Hormonal Contraceptives: Patients treated with JOURNAVX who are taking concomitant hormonal contraceptives containing progestins other than levonorgestrel and norethindrone should use additional nonhormonal contraceptives (such as condoms) or use alternative contraceptives during JOURNAVX treatment and for 28 days after discontinuation of JOURNAVX.

Risk of Adverse Reactions in Patients With Moderate and Severe Hepatic Impairment: Patients with moderate hepatic impairment have higher systemic exposures of suzetrigine and its active metabolite than those with normal hepatic function, which may increase the risk of JOURNAVX-related adverse reactions.

ADVERSE REACTIONS

Pooled adverse reactions from Trials 1 and 2 that occurred in ≥1% of patients treated with JOURNAVX and at a greater rate than patients treated with placebo were pruritus, muscle spasms, increased blood creatine phosphokinase, and rash. The safety profile of JOURNAVX in Trial 3 was consistent with that observed in Trials 1 and 2.

DRUG INTERACTIONS

Effect of Other Drugs on JOURNAVX

CYP3A Inhibitors: A reduced dose is recommended when coadministered with moderate CYP3A inhibitors. Avoid food or drink containing grapefruit.

Strong and Moderate CYP3A Inducers: Avoid concomitant use of JOURNAVX with strong and moderate CYP3A inducers. Concomitant use of strong or moderate CYP3A inducers results in reduced exposures of suzetrigine and its active metabolite, which may result in reduced JOURNAVX efficacy.

Effect of JOURNAVX on Other Drugs

CYP3A Substrates: Dose adjustment of the concomitant CYP3A substrates may be required when initiating or discontinuing JOURNAVX. Discontinuation of JOURNAVX may increase the exposure of sensitive CYP3A substrates.

USE IN SPECIFIC POPULATIONS

Pregnancy

There are no available data on the use of JOURNAVX during pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.

Lactation

There are no data on the presence of suzetrigine or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for JOURNAVX and any potential adverse effects on the breastfed child from JOURNAVX or from the underlying maternal condition.

Infertility

JOURNAVX may reversibly impact the likelihood of females of reproductive potential to become pregnant while on treatment. Patients using contraceptives should continue to use contraceptives.

Geriatric Use

Based on population pharmacokinetic analyses in patients with ages ranging from 18 to 75 years, age does not have a clinically relevant impact on suzetrigine exposure.

Hepatic Impairment

The recommended JOURNAVX dosage is lower in patients with moderate hepatic impairment (Child-Pugh Class B) than those with normal hepatic function. Avoid use of JOURNAVX in patients with severe hepatic impairment (Child-Pugh Class C).

Renal Impairment

Avoid use of JOURNAVX in patients with renal impairment of eGFR <15 mL/min.

Please see full Prescribing Information for JOURNAVX.

References

1. JOURNAVX [prescribing information]. Vertex Pharmaceuticals Incorporated. Boston, MA; January 2025.
2. Osteen JD, Imanisi 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. Published online January 8, 2025. doi:10.1007/s40122-024-00697-0
3. Contet C, Kieffer BL, Befort K. Mu opioid receptor: a gateway to drug addiction. Curr Opin Neurobiol. 2004;14(3):370-378. doi:10.1016/j.conb.2004.05.005
4. Code of Federal Regulations. 21 CFR Part 1308—Schedules of controlled substances. Updated August 8, 2025. Accessed August 12, 2025. https://www.ecfr.gov/current/title-21/chapter-II/part-1308
5. Jones J, Correll DJ, Lechner SM, et al. Selective inhibition of Naᵥ1.8 with VX-548 for acute pain. N Engl J Med. 2023;389(5):393-405. doi:10.1056/NEJMoa2209870
6. Bertoch T, D’Aunno D, McCoun J, et al. Suzetrigine, a non-opioid Naᵥ1.8 inhibitor for treatment of moderate-to-severe acute pain: two phase 3 randomized clinical trials. Anesthesiology. 2025. doi:10.1097/ALN.0000000000005460

JOURNAVX is manufactured for Vertex Pharmaceuticals Incorporated.
JOURNAVX, Vertex, and the Vertex triangle logo are registered trademarks of Vertex Pharmaceuticals Incorporated.
© 2025 Vertex Pharmaceuticals Incorporated | VXR-US-43-2501010 (v1.0) | 10/2025