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, then 900 mg/day (300 mg three times daily) on day 3, with subsequent titration up to 1800 mg/day (600 mg three times daily) as the minimum effective dose, and up to 3600 mg/day (1200 mg three times daily) as the maximum dose if needed for optimal pain relief. 1
Initial Titration Protocol
The FDA-approved dosing schedule provides a rapid 3-day titration to therapeutic levels 1:
- Day 1: 300 mg once daily
- Day 2: 300 mg twice daily (600 mg/day total)
- Day 3: 300 mg three times daily (900 mg/day total)
- Days 4+: Continue titrating upward by 300 mg increments every 1-7 days as tolerated 2, 1
This aggressive initial titration is supported by research showing that starting doses of 600 mg/day provide moderate pain relief with minimal side effects in the first three days of treatment, and that starting with lower doses (200 mg/day) offers no advantage in reducing side effects 3.
Target Therapeutic Dose Range
The minimum effective dose is 1800 mg/day (600 mg three times daily), which should be the initial target for most patients. 2, 1 Clinical trials demonstrated efficacy across the range of 1800-3600 mg/day, though the FDA label notes that additional benefit above 1800 mg/day was not clearly demonstrated in controlled studies 1. However, the number needed to treat (NNT) for gabapentin at up to 3600 mg/day is 4.39, indicating clinically meaningful efficacy at higher doses 4, 2.
The maximum dose is 3600 mg/day (1200 mg three times daily), which may be needed for optimal pain relief in some patients 2, 1.
Critical Dosing Requirements
Administer gabapentin three times daily with a maximum interval of 12 hours between doses. 2, 1 This is non-negotiable due to gabapentin's nonlinear pharmacokinetics from saturable absorption via the L-amino acid transport system in the proximal small intestine 2. Once-daily or twice-daily dosing with standard gabapentin formulations is inadequate and should be avoided 2.
Duration of Therapeutic Trial
Allow 3-8 weeks for titration plus 2 weeks at maximum tolerated dose before declaring treatment failure—potentially requiring 2 months or more for an adequate trial. 2 Efficacy for neuropathic pain develops gradually over several weeks, so premature discontinuation is a common pitfall 2.
Renal Dose Adjustment
Dose adjustment is mandatory in 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 single daily dose
- CrCl <15 mL/min: 100-300 mg/day as single daily dose
- Hemodialysis: Maintenance dose based on CrCl plus supplemental post-dialysis dose of 125-350 mg after each 4-hour session 1
Special Population Considerations
For elderly or medically frail patients, use slower titration with increases by 300 mg every 3-7 days rather than daily increases. 2, 5 Elderly patients have higher risk of falls from dizziness, which is dose-dependent 2. However, age alone should not prevent achieving therapeutic doses, as efficacy and tolerability are comparable in patients ≥65 years versus younger patients 6.
Side Effect Profile and Management
Common side effects include dizziness (23.9%), somnolence (27.4%), dry mouth, and constipation, which are dose-dependent 2, 6. Approximately 80% of patients report somnolence at 2400 mg/day 5. These effects are typically mild to moderate and often transient 5. Starting low and titrating slowly minimizes these effects 2.
Discontinuation Protocol
Never discontinue gabapentin abruptly—taper gradually over at least 1 week to avoid withdrawal symptoms. 2
Alternative Formulations
Extended-release gabapentin formulations (gabapentin ER and gastroretentive gabapentin) allow once-daily dosing but show variable efficacy. Gabapentin ER 1800 mg once daily demonstrates modest efficacy (SMD -0.21) but twice-daily dosing shows no significant effect 7. Gabapentin enacarbil (GEn) at 1200-2400 mg/day may offer better tolerability with lower rates of dizziness and somnolence compared to standard gabapentin 7, though standard three-times-daily gabapentin remains the FDA-approved and most extensively studied formulation for postherpetic neuralgia 1.
Common Pitfalls to Avoid
- Do not use once-daily or twice-daily dosing with standard gabapentin formulations 2
- Do not rush titration in elderly patients due to increased fall risk 2
- Do not stop at 900 mg/day—this is below the minimum effective dose of 1800 mg/day 2, 1
- Do not discontinue prematurely—allow the full 2-month trial period 2
- Do not forget renal dose adjustment—gabapentin is renally eliminated and accumulates in renal impairment 2, 1