What is the appropriate dosage of Gabapentin (Neurontin) for an adult patient with neuropathic pain or epilepsy?

Gabapentin 600 mg Oral Tablet Dosing

For neuropathic pain in adults, start gabapentin at 300 mg once daily on day 1, increase to 300 mg twice daily on day 2, then 300 mg three times daily (900 mg/day total) on day 3, with subsequent titration by 300 mg every 3-7 days to reach the target therapeutic dose of 1800-3600 mg/day divided three times daily. 1, 2

Initial Dosing and Titration Schedule

• Day 1: Begin with 300 mg at bedtime (or 100-300 mg for elderly/frail patients) 1, 2
• Day 2: Increase to 600 mg/day (300 mg twice daily) 2
• Day 3: Advance to 900 mg/day (300 mg three times daily) 1, 2
• Days 4 onward: Titrate upward by 300 mg increments every 3-7 days as tolerated until reaching target dose 1

The FDA label specifies this exact schedule for postherpetic neuralgia, and guidelines extend this approach to other neuropathic pain conditions 2, 1.

Target Therapeutic Dose Range

The minimum effective dose for most neuropathic pain conditions is 1800 mg/day (600 mg three times daily), with a maximum of 3600 mg/day (1200 mg three times daily). 1, 2

• 1800 mg/day (600 mg TID): Minimum effective dose for neuropathic pain; 32-38% of patients achieve ≥50% pain reduction versus 17-21% with placebo 1, 3
• 2400-3600 mg/day: May be needed for optimal pain relief in some patients, though additional benefit above 1800 mg/day is not consistently demonstrated 2, 4
• Three-times-daily dosing is mandatory due to gabapentin's saturable, nonlinear absorption pharmacokinetics; maximum interval between doses should not exceed 12 hours 1, 2

Duration of Adequate Trial

Allow 3-8 weeks for titration plus 2 weeks at maximum tolerated dose before declaring treatment failure; an adequate trial may require 2 months or more. 1, 5

Efficacy for neuropathic pain develops gradually over several weeks, not immediately 1.

Renal Dose Adjustment (Mandatory)

Calculate creatinine clearance using the Cockcroft-Gault equation before initiating therapy, as gabapentin is renally excreted and dose reduction is mandatory in renal impairment. 1, 2

• CrCl ≥60 mL/min: 900-3600 mg/day in three divided doses 2
• CrCl 30-59 mL/min: 400-1400 mg/day in two divided doses 2
• CrCl 15-29 mL/min: 200-700 mg/day as single daily dose 2
• CrCl <15 mL/min: 100-300 mg/day as single daily dose 2
• Hemodialysis: Maintenance dose based on CrCl plus supplemental 125-350 mg post-dialysis 2

Special Population Considerations

Elderly Patients

Start at 100-200 mg/day with slower titration (increases every 3-7 days or longer) in elderly patients due to invariably reduced renal function and increased fall risk from dizziness. 1, 5

• Elderly patients are more susceptible to falls, confusion, and sedation 1
• The effective dose in older adults may be lower than standard ranges 1
• Mandatory renal function assessment before initiation 5

Medically Frail Patients

Use the same conservative approach as elderly patients: start at 100 mg at bedtime and titrate more slowly 1.

Common Adverse Effects

• Dizziness (19%), somnolence (14%), peripheral edema (7%), and gait disturbance (9%) are most common 3, 1
• These effects are typically mild to moderate, dose-dependent, and often transient, usually subsiding within approximately 10 days 1, 4
• Adverse event withdrawals occur in 11% versus 8.2% with placebo (NNH 30) 3
• Higher doses (>600 mg/day) are associated with increased risk of hospitalization with altered mental status in older adults (1.27% vs 1.06% for ≤600 mg/day) 6

Critical Pitfalls to Avoid

• Never start at high doses (such as 800 mg QID) without gradual titration, as this dramatically increases 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 due to saturable absorption 1
• Do not fail to assess renal function before initiating therapy—this is non-negotiable, especially in elderly patients 5
• Do not discontinue abruptly; taper gradually over at least 1 week to avoid withdrawal symptoms 1, 2
• Do not rush titration in elderly patients, as this increases fall risk from dizziness 1
• Do not assume lack of efficacy if adequate time for titration and therapeutic trial has not been allowed (minimum 2 months) 1, 5

Administration

• Administer orally with or without food 2
• If dividing scored 600 mg or 800 mg tablets, take unused half-tablet as next dose; discard unused half-tablets after 28 days 2
• Maximum time between doses should not exceed 12 hours 2