Gabapentin Titration Schedule
Gabapentin should be initiated at 300 mg on day 1, increased to 600 mg/day (300 mg twice daily) on day 2, then to 900 mg/day (300 mg three times daily) on day 3, with subsequent increases of 300 mg every 3–7 days as tolerated until reaching the therapeutic range of 1800–3600 mg/day. 1
Standard Titration Protocol for Adults
The FDA-approved foundation schedule is:
- Day 1: 300 mg once (single dose) 1
- Day 2: 600 mg/day (300 mg twice daily) 1
- Day 3: 900 mg/day (300 mg three times daily) 1
- Day 4 onward: Increase by 300 mg every 3–7 days as tolerated 2, 1
The minimum effective dose for neuropathic pain is 1800 mg/day (600 mg three times daily), and the maximum is 3600 mg/day (1200 mg three times daily). 2
Doses of 1800–3600 mg/day provide moderate-quality evidence for efficacy, with 32–38% of patients achieving ≥50% pain reduction versus 17–21% with placebo. 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 can require 2 months or more because efficacy develops gradually over several weeks. 2
Mandatory Three-Times-Daily Dosing
Gabapentin must be administered three times daily due to its nonlinear, saturable absorption pharmacokinetics; the interval between doses must not exceed 12 hours. 2, 1
Once-daily or twice-daily regimens lead to subtherapeutic levels and treatment failure because higher individual doses saturate the intestinal transporter, reducing bioavailability. 2
Elderly Patient Modifications
In geriatric patients, start at 100–200 mg/day and titrate more slowly with increases every 3–7 days or longer. 2, 3
Elderly individuals experience higher rates of adverse effects:
These effects increase fall risk, so slower titration (every 3–7 days or longer) is mandatory to minimize dizziness-related falls. 2
The effective dose in older adults may be below the standard adult range. 2
Renal Impairment Dose Adjustments
Dose reduction is mandatory based on creatinine clearance (CrCl) because gabapentin is eliminated primarily by renal excretion. 2, 1
Calculate CrCl using the Cockcroft-Gault equation before initiating therapy: 1
CrCl (mL/min) = [(140 − age) × weight in kg] / (72 × serum creatinine in mg/dL)
Multiply by 0.85 for females
| Creatinine Clearance | Total Daily Dose | Dosing Frequency | Titration Speed |
|---|---|---|---|
| ≥60 mL/min | 900–3600 mg | Three times daily | Standard (every 3–7 days) |
| 30–59 mL/min | 400–1400 mg | Twice daily | Slower (every 7+ days) |
| 15–29 mL/min | 200–700 mg | Once daily | Much slower |
| <15 mL/min | 100–300 mg | Once daily | Very slow |
For patients on hemodialysis, administer maintenance doses based on CrCl estimates plus a supplemental post-hemodialysis dose (125–350 mg) after each 4-hour dialysis session. 1
In severe renal impairment (CrCl 15–29 mL/min), start at 100–200 mg once daily with increases every 3–7 days or longer—standard titration schedules must not be used. 3
Critical Pitfalls to Avoid
Never start at high doses (e.g., 800 mg four times daily) without gradual titration—this dramatically increases the risk of intolerable adverse effects, particularly in elderly patients. 3
Do not fail to assess renal function before initiating therapy—this is non-negotiable, especially in older adults, because age-related decline in renal function is often masked by normal serum creatinine due to reduced muscle mass. 2
Do not declare treatment failure before completing the full 2-month trial at therapeutic doses, as efficacy develops gradually over weeks. 2
Never abruptly discontinue gabapentin—taper gradually over a minimum of 1 week (longer periods may be needed) to avoid withdrawal symptoms. 1
Adverse Effect Management
Common side effects include dizziness and somnolence, which are typically mild to moderate, dose-dependent, and often transient, usually subsiding within approximately 10 days from initiation. 2, 4
Starting with lower doses (100–300 mg at bedtime rather than 300 mg three times daily) and implementing gradual titration with adequate intervals (every 3–7 days) minimizes peak-related side effects. 2
Adverse event withdrawals occur in 11% of patients versus 8.2% with placebo (number needed to harm = 30). 2