Gabapentin Dosing Guidelines
Start gabapentin at 300 mg once daily (or at bedtime) on day 1, increase to 600 mg/day (300 mg twice daily) on day 2, then to 900 mg/day (300 mg three times daily) on day 3, and titrate upward by 300 mg every 3–7 days as tolerated to reach the minimum effective dose of 1800 mg/day (600 mg three times daily), with a maximum of 3600 mg/day (1200 mg three times daily). 1, 2
Standard Titration Protocol
Day-by-day initiation:
- Day 1: 300 mg once daily (or at bedtime) 1, 2
- Day 2: 600 mg/day (300 mg twice daily) 1
- Day 3: 900 mg/day (300 mg three times daily) 1, 3
- Days 4 onward: Increase by 300 mg every 3–7 days as tolerated until reaching therapeutic dose 2, 1
Target Therapeutic Dose Range
- Minimum effective dose: 1800 mg/day (600 mg three times daily) 2, 3
- Standard therapeutic range: 1800–3600 mg/day in three divided doses 2, 1
- Maximum dose: 3600 mg/day (1200 mg three times daily) 1, 2
Evidence for efficacy: At doses of 1800–3600 mg/day, 32–38% of patients achieve at least 50% pain reduction versus 17–21% with placebo in postherpetic neuralgia and painful diabetic neuropathy (NNT 5.9–6.7). 2, 4
Mandatory Three-Times-Daily Dosing
Gabapentin MUST be administered three times daily because of its nonlinear, saturable absorption pharmacokinetics; the maximum interval between doses must not exceed 12 hours. 1, 2 Once-daily or twice-daily regimens lead to subtherapeutic levels and treatment failure. 2
Duration of Adequate Trial
Allow 3–8 weeks for titration plus an additional 2 weeks at the maximum tolerated dose before declaring treatment failure—an adequate trial may require 2 months or more because efficacy develops gradually over several weeks. 2, 3
Elderly Patient Adjustments
Start at 100–200 mg/day in elderly patients and titrate more slowly with increases every 3–7 days (or longer) to reduce fall risk from dizziness. 2, 5
- Elderly patients experience higher rates of adverse effects: dizziness (19%), somnolence (14%), peripheral edema (7%), and gait disturbance (9%). 5
- The effective dose in older adults may be lower than the standard adult range. 2
- Always calculate creatinine clearance before initiating therapy in elderly patients, as age-related renal decline is often masked by normal serum creatinine due to reduced muscle mass. 5
Renal Impairment Dose Adjustments
Dose reduction is mandatory based on creatinine clearance because gabapentin is eliminated primarily by renal excretion. 1, 2
| Creatinine Clearance (mL/min) | Total Daily Dose (mg/day) | Dosing Frequency |
|---|---|---|
| ≥60 | 900–3600 | 300–1200 mg TID |
| 30–59 | 400–1400 | 200–700 mg BID |
| 15–29 | 200–700 | 200–700 mg QD |
| <15 | 100–300 | 100–300 mg QD |
| Hemodialysis | Maintenance dose based on CLcr + supplemental post-dialysis dose (125–350 mg after each 4-hour session) | Variable |
Calculate creatinine clearance using the Cockcroft-Gault equation: CLcr (mL/min) = [(140 - age) × weight in kg] / (72 × serum creatinine in mg/dL), multiplied by 0.85 for females. 1
Common Adverse Effects
- Dizziness (19%), somnolence (14%), peripheral edema (7%), gait disturbance (9%) are the most common adverse effects. 5, 4
- These effects are typically mild to moderate, dose-dependent, and often transient, usually subsiding within approximately 10 days. 3, 6
- Adverse event withdrawals: 11% with gabapentin versus 8.2% with placebo (NNH 30). 4, 2
Critical Pitfalls to Avoid
- Never start at high doses (such as 800 mg four times daily) without gradual titration—this dramatically increases the risk of intolerable adverse effects, particularly in elderly patients. 5
- Do not use once-daily or twice-daily dosing for standard gabapentin—three-times-daily administration is essential. 2
- Do not rush titration in elderly patients—slower dose increments (every 3–7 days or longer) reduce dizziness-related fall risk. 2
- Do not discontinue abruptly—taper gradually over at least 1 week to avoid withdrawal symptoms. 1, 2
- Do not declare treatment failure before completing the full 2-month trial at therapeutic doses, as efficacy develops gradually over weeks. 2
- Never assume normal renal function in elderly patients based on serum creatinine alone—always calculate creatinine clearance. 5