Gabapentin Dosing Schedule
Start gabapentin at 300 mg once daily (or at bedtime), increase to 300 mg three times daily (900 mg/day) by day 3, then titrate upward by 300 mg every 3-7 days until reaching the target therapeutic dose of 1800-3600 mg/day in three divided doses. 1, 2
Standard Titration Protocol
The FDA-approved dosing schedule follows a rapid initial titration for most indications 2:
- Day 1: 300 mg once daily (single dose)
- Day 2: 600 mg/day (300 mg twice daily)
- Day 3: 900 mg/day (300 mg three times daily)
- Days 4+: Continue increasing by 300 mg increments every 3-7 days as tolerated 1, 2
Target therapeutic dose: 1800-3600 mg/day divided into three daily doses (600-1200 mg three times daily) 1, 2
Critical Dosing Principles
Three-times-daily dosing is mandatory due to gabapentin's nonlinear, saturable absorption pharmacokinetics—once or twice daily dosing is inadequate for therapeutic effect 1. The maximum interval between doses should not exceed 12 hours 2.
Gabapentin has dose-dependent absorption that becomes less efficient at higher single doses, making gradual titration with divided dosing essential for achieving therapeutic blood levels 1, 3.
Slower Titration for Vulnerable Populations
Elderly or medically frail patients require more conservative titration 1:
- Start at 100-300 mg at bedtime
- Increase by 100-300 mg every 3-7 days (longer intervals preferred)
- This slower approach reduces fall risk from dizziness, which occurs in approximately 19% of patients 1, 4
Adequate Trial Duration
Allow 3-8 weeks for titration plus 2 weeks at maximum tolerated dose before declaring treatment failure—an adequate therapeutic trial may require 2 months or more 1. This extended timeline is necessary because gabapentin's efficacy for neuropathic pain develops gradually over several weeks 1.
Renal Dose Adjustment (Mandatory)
Gabapentin is eliminated unchanged by the kidneys, requiring dose reduction based on creatinine clearance 2:
- CrCl ≥60 mL/min: 900-3600 mg/day (300-1200 mg three times daily)
- CrCl 30-59 mL/min: 400-1400 mg/day (200-700 mg twice daily)
- CrCl 15-29 mL/min: 200-700 mg/day (200-700 mg once daily)
- CrCl <15 mL/min: 100-300 mg/day (100-300 mg once daily)
- Hemodialysis patients: Maintenance dose based on CrCl plus supplemental 125-350 mg post-dialysis 2
Evidence-Based Efficacy Thresholds
For postherpetic neuralgia and diabetic neuropathy, doses of 1800-3600 mg/day demonstrate moderate-quality evidence for efficacy 4:
- 32-38% of patients achieve substantial benefit (≥50% pain reduction) versus 17-21% with placebo (NNT 5.9-6.7) 4
- 46-52% achieve moderate benefit (≥30% pain reduction) versus 25-37% with placebo (NNT 4.8-6.6) 4
The additional benefit of doses exceeding 1800 mg/day has not been consistently demonstrated in clinical trials, though doses up to 3600 mg/day are well-tolerated 2, 4.
Common Pitfalls to Avoid
Do not rush titration in elderly patients—this significantly increases fall and fracture risk, with a clear dose-response relationship showing highest risk at doses ≥2400 mg/day (RR 1.90) 5.
Do not discontinue abruptly—taper gradually over a minimum of 1 week to avoid withdrawal symptoms 1, 2. Longer tapering periods may be needed at prescriber discretion 2.
Do not use inadequate dosing schedules—the very low doses described in early case reports (100 mg 2-3 times daily) are not biologically plausible given that target therapeutic doses are 1800-3600 mg/day 6.
Adverse Effect Profile
Expect dose-dependent adverse effects 4, 5:
- Dizziness: 19% of patients
- Somnolence: 14% of patients
- Peripheral edema: 7% of patients
- Gait disturbance: 14% of patients
- Adverse event withdrawals: 11% versus 8.2% with placebo (NNH 30) 4
These effects are typically mild to moderate and often transient with continued therapy 1.
Condition-Specific Considerations
For HIV-associated neuropathic pain, gabapentin is recommended as first-line oral therapy, titrated to a maximum of 2400 mg/day over 4 weeks in divided doses 6, 1. However, evidence quality is limited by small trial sizes and high placebo response rates (29.8% pain reduction) 6.
For chemotherapy-induced peripheral neuropathy, current evidence does not support routine gabapentin use—multiple trials have failed to demonstrate benefit, and insurance requirements mandating gabapentin trial before duloxetine contradict guideline recommendations 6.