Gabapentin Dosing for Postherpetic Neuralgia
For postherpetic neuralgia, initiate gabapentin at 300 mg on Day 1, increase to 600 mg/day (300 mg twice daily) on Day 2, and 900 mg/day (300 mg three times daily) on Day 3, with subsequent titration to 1800 mg/day (600 mg three times daily) as the target maintenance dose. 1
Initial Titration Schedule
The FDA-approved dosing regimen provides a structured 3-day initiation protocol 1:
- Day 1: 300 mg as a single dose
- 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 the dose as needed for pain relief up to 1800 mg/day divided into three doses (600 mg three times daily). 1
Target Maintenance Dose
The recommended maintenance dose is 1800 mg/day (600 mg three times daily), which represents the optimal balance between efficacy and tolerability. 1 Clinical trials demonstrated efficacy across a range of 1800-3600 mg/day, but doses above 1800 mg/day did not show additional benefit in controlled studies. 1
The Mayo Clinic guidelines support this approach, recommending initiation at 100-300 mg at bedtime or 100-300 mg three times daily, with increases of 100-300 mg every 1-7 days as tolerated, up to a maximum of 3600 mg/day in three divided doses. 2 However, an adequate trial requires 3-8 weeks for titration plus 2 weeks at maximum dose—meaning treatment trials can require 2 months or more. 2
Maximum Dosing
While the FDA label indicates that doses up to 3600 mg/day have been studied and are well-tolerated 1, the additional benefit of doses exceeding 1800 mg/day was not demonstrated in clinical trials. 1 Multiple guidelines confirm that the usual maximum analgesic dose ranges from 1800-3600 mg/day. 2
The evidence shows gabapentin at up to 3600 mg/day significantly decreased pain compared to placebo in a randomized trial of 563 PHN patients, with a number needed to treat (NNT) of 4.39. 2 Another trial found 900 mg gabapentin resulted in 66% decreased pain and allodynia compared to 33% with placebo. 2
Dosing Frequency
Administer gabapentin three times daily with a maximum interval of 12 hours between doses. 1 This frequent dosing is necessary due to gabapentin's nonlinear pharmacokinetics from saturable absorption via the L-amino acid transport system in the proximal small intestine. 2
Special Populations
Renal Impairment
Dose adjustment is mandatory in patients with renal dysfunction 2, 1:
- CrCl ≥60 mL/min: 900-3600 mg/day in three divided doses
- CrCl 30-59 mL/min: 400-1400 mg/day in two divided doses
- CrCl 15-29 mL/min: 200-700 mg/day as a single daily dose
- CrCl <15 mL/min: 100-300 mg/day as a single daily dose
- Hemodialysis: Maintenance dose based on CrCl plus supplemental post-dialysis dose of 125-350 mg after each 4-hour session 1
Elderly Patients
Exercise caution in dose selection for elderly patients due to age-related decline in renal function. 1 Consider lower starting doses and slower titration. 2 One study in elderly gabapentin-naive patients found that 600 mg/day could be a safe and effective starting dose, as minimal doses of 200 mg/day did not offer better side effect reduction. 3
Common Pitfalls
The most common mistake is inadequate dose titration or insufficient trial duration. Gabapentin requires careful, gradual titration over weeks, and an adequate trial demands at least 2 months. 2 Premature discontinuation before reaching therapeutic doses or adequate trial duration leads to treatment failure.
Side effects—particularly dizziness, somnolence, dry mouth, and constipation—are dose-dependent and can be minimized by starting low and titrating slowly. 2 Approximately 80% of patients report somnolence, which may actually improve sleep scores in PHN patients. 2
Alternative Formulation
A once-daily gastroretentive gabapentin formulation exists, providing gradual release to optimize absorption and potentially reduce dizziness and somnolence compared to immediate-release formulations. 4 However, the standard three-times-daily formulation remains the FDA-approved and most widely studied regimen for PHN. 1