Gabapentin Dosing for Postherpetic Neuralgia
Start gabapentin at 300 mg on day 1, increase to 600 mg/day (300 mg twice daily) on day 2, then 900 mg/day (300 mg three times daily) on day 3, and titrate up to 1800 mg/day (600 mg three times daily) as the target maintenance dose, with a maximum of 3600 mg/day in three divided doses if needed, though doses above 1800 mg/day provide no additional demonstrated benefit. 1
Initial Dosing Schedule
The FDA-approved titration schedule for postherpetic neuralgia follows a rapid 3-day escalation 1:
- Day 1: 300 mg once daily
- Day 2: 600 mg/day (300 mg twice daily)
- Day 3: 900 mg/day (300 mg three times daily)
After this initial titration, continue increasing by 100-300 mg every 1-7 days as tolerated until reaching the target dose 2.
Target and Maximum Dosing
- Target maintenance dose: 1800 mg/day (600 mg three times daily) 1
- Effective dose range: 1800-3600 mg/day 1, 3
- Maximum dose: 3600 mg/day in three divided doses 2, 1
Clinical trials demonstrated comparable efficacy across the 1800-3600 mg/day range, with no additional benefit shown above 1800 mg/day 1. This is a critical point—while higher doses are FDA-approved and well-tolerated, they do not improve pain outcomes and increase adverse effects 2.
Duration of Adequate Trial
An adequate trial requires 3-8 weeks for titration plus 2 weeks at maximum tolerated dose 2. This means gabapentin therapy can require 2 months or more to properly assess efficacy 2. This extended timeline is essential because premature discontinuation may miss therapeutic benefit.
Dosing Intervals and Pharmacokinetic Considerations
Gabapentin has nonlinear pharmacokinetics due to saturable absorption in the proximal small intestine 2. This saturable L-amino acid transport system means that higher individual doses are not proportionally absorbed, necessitating divided dosing throughout the day 4.
Renal Dose Adjustments
Dosage reduction is mandatory in renal insufficiency 2. For creatinine clearance 1:
- ≥60 mL/min: 900-3600 mg/day (300-1200 mg three times daily)
- 30-59 mL/min: 400-1400 mg/day (200-700 mg twice daily)
- 15-29 mL/min: 200-700 mg/day (100-700 mg once daily)
- <15 mL/min: 100-300 mg once daily
- Hemodialysis patients: Maintenance dose based on creatinine clearance plus supplemental post-dialysis dose of 125-350 mg after each 4-hour session 1
Special Population Considerations
Elderly patients require lower starting doses and slower titration 2. Given that elderly patients are more likely to have decreased renal function, dose selection should be based on creatinine clearance values 1. The high incidence of dizziness and somnolence with gabapentin is particularly problematic in this population 5, 6.
Common Adverse Effects and Tolerability
The most frequent dose-dependent adverse effects are 2:
- Dizziness
- Sedation/somnolence
- Peripheral edema
- Ataxia
These effects can be minimized by starting with lower dosages and titrating cautiously 2. In clinical trials, somnolence, dizziness, ataxia, peripheral edema, and infection were more frequent with gabapentin, though withdrawal rates were comparable to placebo (13.3% vs 9.5%) 3.
Clinical Efficacy Evidence
In the pivotal trial, gabapentin reduced average daily pain scores from 6.3 to 4.2 points compared to 6.5 to 6.0 points with placebo (P<0.001) 3. Secondary outcomes including sleep interference, quality of life measures, and mood also significantly improved 3. The American College of Physicians recommends gabapentin as first-line oral pharmacological treatment for postherpetic neuralgia 5.
Critical Pitfalls to Avoid
- Do not expect benefit above 1800 mg/day - Higher doses increase adverse effects without improving pain control 1
- Do not undertitrate - The full 1800 mg/day target is necessary for most patients to achieve benefit 5
- Do not assess efficacy prematurely - Allow the full 2-month trial period before declaring treatment failure 2
- Do not forget renal adjustment - Failure to reduce doses in renal insufficiency leads to toxicity 2, 1
- Do not use for prevention - Gabapentin initiated during acute herpes zoster does not prevent postherpetic neuralgia development 7, 8