What is the recommended treatment approach for a patient with chronic neuropathic pain using Suzetrigine (no generic name mentioned), considering potential side effects and alternative treatment options like gabapentin or pregabalin?

Suzetrigine for Chronic Neuropathic Pain

Suzetrigine should not be used as first-line treatment for chronic neuropathic pain; instead, start with gabapentin (1800-3600 mg/day) or pregabalin (150-600 mg/day), as these medications have robust evidence for efficacy in chronic neuropathic pain conditions, while suzetrigine currently has FDA approval only for acute pain and lacks any evidence for chronic pain management. 1, 2

Current Evidence Status for Suzetrigine

• Suzetrigine is a selective NaV1.8 sodium channel blocker recently FDA-approved, but only for acute postoperative pain, not chronic neuropathic pain 3
• The only published evidence is a single case report in a 16-year-old with hereditary neuropathy undergoing foot surgery, where pain rapidly intensified within 24 hours of stopping the medication 3
• No randomized controlled trials exist for suzetrigine in chronic neuropathic pain conditions such as diabetic neuropathy, postherpetic neuralgia, or HIV-associated neuropathy 3

Recommended First-Line Treatment Algorithm

Start with Gabapentin or Pregabalin

Gabapentin dosing protocol: 1, 4

• Day 1: 300 mg at bedtime
• Day 2: 300 mg twice daily (600 mg/day)
• Day 3: 300 mg three times daily (900 mg/day)
• Titrate by 300 mg every 3-7 days as tolerated
• Target dose: 1800-3600 mg/day in three divided doses
• Allow 3-8 weeks for titration plus 2 weeks at maximum tolerated dose for adequate trial 1

Pregabalin dosing protocol (simpler titration): 1, 5

• Start: 50 mg three times daily or 75 mg twice daily
• Increase to 300 mg/day after 3-7 days
• Further titrate by 150 mg/day every 3-7 days as tolerated
• Target dose: 300-600 mg/day in divided doses
• Assess efficacy after 4 weeks 5

Expected Efficacy with First-Line Agents

For postherpetic neuralgia: 2

• 32% achieve substantial benefit (≥50% pain relief) with gabapentin vs 17% with placebo (NNT 6.7)
• 46% achieve moderate benefit (≥30% pain relief) with gabapentin vs 25% with placebo (NNT 4.8)

For painful diabetic neuropathy: 2

• 38% achieve substantial benefit with gabapentin vs 21% with placebo (NNT 5.9)
• 52% achieve moderate benefit with gabapentin vs 37% with placebo (NNT 6.6)

Second-Line Options if First-Line Fails

If inadequate response to gabapentin or pregabalin after adequate trial: 1

1. Tricyclic antidepressants (nortriptyline or desipramine): 1

   • Start 25 mg at bedtime
   • Increase by 25 mg every 3-7 days as tolerated
   • Maximum 150 mg/day
   • Obtain screening ECG for patients >40 years old 1
   • Contraindicated in hepatic disease 5

2. Duloxetine (SSNRI): 1

   • Start 30 mg once daily for 1 week
   • Increase to 60 mg once daily
   • Maximum 60 mg twice daily
   • Contraindicated in hepatic disease 5

3. Topical lidocaine 5% patches (for localized pain): 1

   • Maximum 3 patches daily for 12-18 hours
   • Particularly useful in elderly patients due to lack of systemic effects 1
   • Most appropriate for well-localized peripheral neuropathic pain 1

Third-Line: Opioids (Use with Extreme Caution)

Opioids should NOT be first-line for chronic neuropathic pain 1, 6

• Reserve for patients who fail first-line therapies with moderate to severe pain 1
• Start with lowest effective dose, combining short- and long-acting formulations 1
• Consider morphine plus gabapentin combination for additive effects and lower individual doses 1
• Specific concerns in HIV patients: potential pronociception through CXCR4 upregulation, cognitive impairment, respiratory depression, and addiction risk 1

Critical Safety Considerations

Common adverse effects of gabapentin/pregabalin: 1, 2

• Dizziness (19%), somnolence (14%), peripheral edema (7%), gait disturbance (14%)
• Typically mild to moderate and subside within 10 days 4
• Dose reduction required in renal insufficiency 1

Adverse event withdrawal rates: 2

• Gabapentin: 11% vs placebo 8.2% (NNH 30)
• Serious adverse events similar to placebo (3.2% vs 2.8%)

Key Clinical Pitfalls to Avoid

• Do not use suzetrigine for chronic pain - it lacks evidence and FDA approval for this indication 3
• Do not undertitrate gabapentin - doses of 1800-3600 mg/day are needed for efficacy; 900 mg/day is insufficient 4, 2, 7
• Do not rush titration - allow adequate time (3-8 weeks) to reach therapeutic doses and assess response 1
• Do not prescribe opioids first-line - they carry significant risks without superior efficacy to gabapentinoids 1, 6
• Do not use TCAs or duloxetine in liver disease - pregabalin or gabapentin are safer alternatives 5