What are the treatment options for postherpetic neuralgia in a patient with an allergy to Lyrica (pregabalin)?

Treatment of Post-Herpetic Neuralgia with Pregabalin Allergy

Recommended First-Line Treatment

Start with gabapentin as your primary oral agent, beginning at 300 mg on day 1,600 mg on day 2, and 900 mg on day 3, then titrate to 1800-3600 mg/day in three divided doses, as this is the recommended first-line treatment by the American College of Physicians and has demonstrated efficacy across this dose range. 1, 2

• Gabapentin provides significant pain reduction, with studies showing a decrease in average daily pain scores from 6.3 to 4.2 points compared to placebo (6.5 to 6.0 points), with statistical significance (P<0.001). 3
• The maximum time between doses should not exceed 12 hours, requiring three-times-daily dosing. 2
• Efficacy is demonstrated across doses from 1800-3600 mg/day, though additional benefit above 1800 mg/day has not been proven. 2
• Common side effects include somnolence (27.4%), dizziness (23.9%), and ataxia (7.1%), which may be dose-limiting. 4

Alternative First-Line Options

Topical Lidocaine 5% Patch

Apply topical lidocaine 5% patches to the affected area for 12-24 hours daily, as this provides excellent pain relief (NNT = 2) with minimal systemic absorption, making it particularly suitable for elderly patients or those with comorbidities. 5, 1

• Up to four patches can be safely used in 24 hours with systemic lidocaine levels remaining within safe range. 5
• Adverse reactions are rare, mild, and mostly limited to skin rash. 5
• Contraindicated only in advanced liver failure due to decreased lidocaine clearance. 5

Tricyclic Antidepressants

Consider nortriptyline starting at 10-25 mg at bedtime, increasing every 3-7 days to a final dose of 25-100 mg at bedtime, as TCAs have excellent efficacy (NNT = 2.64) with nortriptyline offering better tolerability than amitriptyline. 1

• Nortriptyline provides equivalent analgesic benefit to amitriptyline with improved tolerability. 1
• In elderly patients, start at very low doses (10 mg/day) and do not exceed 75 mg/day due to anticholinergic effects and cardiac risks. 6
• Bedtime dosing minimizes daytime sedation effects. 1

Second-Line Treatment Options

Capsaicin

• The 8% dermal patch or cream provides pain relief for at least 12 weeks. 1
• Apply 4% lidocaine for 60 minutes before capsaicin application to mitigate erythema and pain side effects. 1

Opioids (Use with Caution)

• Oxycodone, extended-release morphine, or methadone show efficacy (NNT = 2.67) but should not be first-line due to risks of pronociception, cognitive impairment, respiratory depression, endocrine/immunological changes, and potential for misuse and addiction. 1
• Tramadol demonstrates efficacy with NNT of 4.76 as a potentially safer opioid alternative. 1

SNRIs

• Duloxetine (60 mg/day) or venlafaxine (150-225 mg/day) may be considered if gabapentin provides inadequate response. 6

Combination Therapy Strategy

If single agents provide inadequate relief, combine morphine with gabapentin, as this allows for lower doses of each medication while providing additive effects. 1

Special Considerations for Elderly Patients

• Assess renal function before starting gabapentin and adjust dose based on creatinine clearance to minimize adverse effects. 6
• For creatinine clearance 30-59 mL/min: reduce to 400-1400 mg/day in two divided doses. 2
• For creatinine clearance 15-29 mL/min: reduce to 200-700 mg/day as single daily dose. 2
• For creatinine clearance <15 mL/min: reduce to 100-300 mg/day as single daily dose. 2
• Patients on hemodialysis require supplemental post-dialysis dosing of 125-350 mg after each 4-hour session. 2

Non-Pharmacological Adjuncts

• Cognitive behavioral therapy, hypnosis, and physical/occupational therapy provide beneficial adjunctive treatment. 1
• These approaches should complement, not replace, pharmacological management. 1

Common Pitfalls to Avoid

• Do not use lamotrigine for PHN due to lack of convincing efficacy evidence and risk of lamotrigine-associated rash. 1
• Avoid exceeding 12-hour intervals between gabapentin doses, as this reduces efficacy. 2
• Monitor elderly patients closely for somnolence, dizziness, and mental clouding with gabapentinoids. 1
• Do not use benzodiazepines for pain relief, as they lack direct analgesic effect and carry high risk in older adults. 5

Treatment Algorithm

1. Start with gabapentin (titrate as described above) OR topical lidocaine patches (especially if localized pain or elderly patient). 1, 2
2. Add nortriptyline if partial response to gabapentin, starting at low dose and titrating slowly. 1
3. Consider combination therapy (gabapentin + opioid) if monotherapy inadequate. 1
4. Incorporate non-pharmacological approaches (CBT, physical therapy) throughout treatment. 1
5. Reassess periodically, as PHN may improve over time and medication adjustments may be needed. 1