Is suzetrigine effective for treating radicular pain?

Suzetrigine for Radicular Pain

Suzetrigine (JOURNAVX) is a novel, FDA-approved non-opioid analgesic that shows promise for treating radicular pain, though it has not been specifically studied in radiculopathy trials and should be considered as an alternative when conventional treatments fail or are contraindicated. 1

What is Suzetrigine?

Suzetrigine is a selective NaV1.8 voltage-gated sodium channel inhibitor that works by blocking pain signal transmission in peripheral sensory neurons, including dorsal root ganglion neurons. 1, 2 Unlike opioids, it has no CNS activity, no addictive potential, and does not cause typical opioid side effects such as respiratory depression or dependence. 3, 2

• The drug is FDA-approved for moderate-to-severe acute pain, with dosing of 100 mg initially followed by 50 mg every 12 hours. 1
• Its major active metabolite (M6-SUZ) is 3.7-fold less potent than suzetrigine but contributes to overall analgesic effect. 1

Evidence for Pain Conditions

Acute Pain Studies

• Phase 3 trials demonstrated statistically significant and clinically meaningful pain reduction in moderate-to-severe acute surgical and non-surgical pain compared to placebo. 3
• In a single-arm study of 256 participants with various acute pain conditions, 83.2% rated suzetrigine's effectiveness as good, very good, or excellent. 3
• The drug was generally safe and well-tolerated, with most adverse events being mild (27.7%) or moderate (8.2%) in severity. 3

Specific Evidence for Radicular Pain

• Clinical trials included patients with lumbar radiculopathy, showing statistically and clinically significant analgesic effects. 4
• However, the mechanism of action suggests incomplete analgesia is possible—even with >99% NaV1.8 inhibition, human dorsal root ganglion neurons can continue firing repetitively due to large baseline NaV1.8 currents and contribution from NaV1.7 channels. 5

How Suzetrigine Fits into Radicular Pain Management

Current Standard Approach

Based on established guidelines, the treatment algorithm for radicular pain prioritizes:

1. First-line: NSAIDs for inflammatory component 6, 7
2. Add gabapentin for neuropathic component (1200-3600 mg/day titrated) 6, 7
3. Consider duloxetine (moderate evidence for small improvements in pain and function) 6
4. Avoid: Systemic corticosteroids (ineffective), benzodiazepines (no benefit, worse outcomes) 6, 7
5. Use opioids cautiously: Lowest dose, shortest duration, with close monitoring 8, 6

Where Suzetrigine Could Be Used

• As an alternative to opioids when non-opioid options are needed but gabapentin/duloxetine are insufficient or contraindicated. 4, 3
• In opioid-restricted settings or patients with opioid contraindications, history of substance use disorder, or intolerance. 4
• For acute exacerbations of radicular pain requiring short-term (up to 14 days) intensive analgesia without opioid risks. 1, 3

Dosing and Administration

• Standard dosing: 100 mg loading dose, then 50 mg every 12 hours for up to 14 days or until pain resolution. 1
• Can be taken with or without food (second dose onward); food delays initial absorption but does not affect overall exposure. 1
• Moderate hepatic impairment (Child-Pugh B): Use reduced dosage (specific dose not provided in label). 1
• Severe hepatic impairment (Child-Pugh C): Avoid use. 1
• Renal impairment: Safe if eGFR ≥15 mL/min; avoid if eGFR <15 mL/min. 1

Safety Profile

Advantages Over Opioids

• No CNS depression, respiratory depression, or addictive potential. 3, 2
• No evidence of dependence or withdrawal in nonclinical studies. 2
• Does not prolong QTc interval at therapeutic doses. 1

Common Adverse Events

• Mild and infrequent: nausea, headache, constipation. 4
• Most adverse events were mild (27.7%) or moderate (8.2%) in severity. 3

Drug Interactions

• Primarily metabolized by CYP3A; potential for interactions with strong CYP3A inhibitors/inducers (though specific guidance not provided in available evidence). 1

Critical Limitations and Caveats

• Not specifically studied in chronic radiculopathy: All major trials focused on acute pain conditions, with treatment duration limited to 14 days. 1, 3
• Incomplete pain relief possible: Due to the mechanism of action, some patients may experience persistent firing of pain neurons despite NaV1.8 inhibition, particularly those with large baseline NaV1.8 currents or significant NaV1.7 contribution. 5
• No head-to-head comparisons with gabapentin, duloxetine, or other standard radiculopathy treatments exist. 4, 3
• Limited long-term safety data: Maximum studied duration is 14 days. 1, 3

Practical Algorithm for Considering Suzetrigine

For acute radicular pain exacerbations:

1. Start with NSAIDs + gabapentin per standard guidelines 6, 7
2. If inadequate relief and opioids are being considered, trial suzetrigine instead (100 mg then 50 mg q12h) 1, 3
3. Reassess at 48-72 hours; if no improvement, consider image-guided steroid injection or other interventions 8, 6

For patients with opioid contraindications:

1. Use suzetrigine as a bridge therapy while optimizing gabapentin/duloxetine dosing 1, 4
2. Limit to 14 days maximum 1
3. Transition to long-term neuropathic pain management strategies 6, 7

Do not use suzetrigine:

• As first-line therapy (insufficient evidence vs. established treatments) 6, 7
• For chronic radicular pain beyond 14 days (no data) 1, 3
• In severe hepatic impairment or eGFR <15 mL/min 1