JOURNAVXTM is the first and only pain signal inhibitor highly selective for NaV1.81,2
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HOW PAIN WORKS
Sodium channel NaV1.8 plays a key role in pain signal transmission3
In response to noxious stimuli, nociceptors (pain-sensing neurons) in the peripheral nervous system (PNS) generate pain signals in the form of action potentials that move along the nerve fibers.3-6 Action potentials travel through the PNS to the central nervous system (CNS), where the brain perceives them as pain.3-5
To generate an action potential, sodium ions enter the neuron through voltage-gated sodium channels, or NaVs.7
NaV1.8 is selectively expressed in peripheral nociceptive neurons, where its role is to transmit action potentials.1,2
NaV1.8 is not expressed in the human brain2
Signals are everywhere, from satellites to stoplights.
They transmit vital information about the world outside us and within, including when it comes to pain.
When the body is injured or experiences tissue damage, pain signals are generated that travel from the site of pain to the brain.
In the brain, those signals are interpreted to create the sensation of pain.
But what if we could inhibit pain signals before they reach the brain?
That’s what JOURNAVX is designed to do.
JOURNAVX is a nonopioid pain signal inhibitor that selectively targets NaV1.8, a voltage-gated sodium channel responsible for transmitting pain signals in peripheral sensory neurons, including the dorsal root ganglia.
In response to noxious stimuli, peripheral pain-sensing neurons, or nociceptors, create pain signals in the form of action potentials that move along the nerve fibers.
To initiate an action potential, sodium ions enter the neuron through voltage-gated sodium channels, or NaVs.
One particular sodium channel, NaV1.8, is predominantly expressed in peripheral sensory neurons and is responsible for transmitting pain signals in the peripheral nervous system.
NaV1.8 is not expressed in the human brain or spinal cord.
By selectively inhibiting NaV1.8, JOURNAVX inhibits sodium ions from entering pain-sensing neurons.
This disrupts the initiation and propagation of action potentials and reduces pain signal transmission from the peripheral nervous system to the central nervous system.
Importantly, JOURNAVX does not interact with μ-opioid receptors in the brain, which are associated with addiction. There is no evidence that JOURNAVX has addictive potential based on available data, including the MOA, preclinical data, and clinical adverse event data.
Yes, signals are all around us. But when it comes to moderate-to-severe acute pain, JOURNAVX inhibits pain signals where they start.
Where pain starts, JOURNAVX begins.
By inhibiting NaV1.8, 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 CNS1,2
Because JOURNAVX is a highly selective inhibitor of NaV1.8 (≥31,000x more selective of NaV1.8 than all other NaV subtypes as measured in vitro), it inhibits pain signal transmission to the spinal cord and brain1,2
JOURNAVX does not interact with µ receptors, which are associated with addiction.2,8 There is no evidence that JOURNAVX has addictive potential based on available data, including the MOA, preclinical data, and clinical adverse event data2
JOURNAVX is not a controlled substance9
References: 1. JOURNAVX [prescribing information]. Vertex Pharmaceuticals Incorporated. Boston, MA; January 2025. 2. 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. Published online January 8, 2025. doi:10.1007/s40122-024-00697-0 3. England S. Voltage-gated sodium channels: the search for subtype-selective analgesics. Expert Opin Investig Drugs. 2008;17(12):1849-1864. doi:10.1517/13543780802514559 4. de Lera Ruiz M, Kraus RL. Voltage-gated sodium channels: structure, function, pharmacology, and clinical indications. J Med Chem. 2015;58(18):7093-7118. doi:10.1021/jm501981g 5. Waxman SG. Targeting a peripheral sodium channel to treat pain. N Engl J Med. 2023;389(5):466-469. doi:10.1056/NEJMe2305708 6. Garland EL. Pain processing in the human nervous system: a selective review of nociceptive and biobehavioral pathways. Prim Care. 2012;39(3):561-571. doi:10.1016/j.pop.2012.06.01 7. Catteral WA. Voltage-gated sodium channels at 60: structure, function and pathophysiology. J Physiol. 2012;590(11):2577-2589. doi:10.1113/jphysiol.2011.224204 8. 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 9. Code of Federal Regulations. 21 CFR Part 1308—Schedules of controlled substances. Updated February 13, 2025. Accessed March 1, 2025. https://www.ecfr.gov/current/title-21/chapter-II/part-1308
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
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.