What is the typical dosing regimen for gabapentin (Neurontin) in adults with neuropathic pain or epilepsy?

Gabapentin Dosing for Neuropathic Pain and Epilepsy

Start gabapentin at 300 mg at bedtime 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, and 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

Initial Titration Protocol

The FDA-approved dosing schedule for postherpetic neuralgia provides the clearest starting framework: 1

• Day 1: 300 mg once at bedtime
• Day 2: 300 mg twice daily (600 mg/day total)
• Day 3: 300 mg three times daily (900 mg/day total)
• Days 4+: Increase by 300 mg every 3-7 days as tolerated 2, 1

This rapid initial titration can be slowed in elderly or medically frail patients, with increases every 3-7 days rather than daily. 3, 2

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 dose of 3600 mg/day (1200 mg three times daily) often needed for optimal pain relief. 2, 1

• For postherpetic neuralgia and painful diabetic neuropathy, 32-38% of patients achieve at least 50% pain reduction at doses of 1800-3600 mg/day, compared to 17-21% with placebo 4
• The FDA label states that efficacy was demonstrated across the 1800-3600 mg/day range, though additional benefit above 1800 mg/day was not consistently demonstrated in clinical trials 1
• Most patients require 1800-3600 mg/day for optimal pain relief 5

Administration Schedule

Gabapentin must be administered three times daily due to its nonlinear, saturable absorption pharmacokinetics. 2, 1

• The maximum time interval between doses should not exceed 12 hours 1
• Once-daily or twice-daily dosing is inadequate for standard gabapentin formulations 2
• Gabapentin can be taken with or without food 1

Dosing for Epilepsy (Partial Onset Seizures)

For patients 12 years and older with epilepsy: 1

• Starting dose: 300 mg three times daily
• Maintenance dose: 300-600 mg three times daily
• Maximum studied dose: 2400 mg/day (well tolerated in long-term studies); doses up to 3600 mg/day have been administered short-term 1

Renal Dose Adjustments

Mandatory dose reduction is required for patients with creatinine clearance below 60 mL/min, as gabapentin is eliminated unchanged by the kidneys. 2, 1

The FDA provides specific dosing based on creatinine clearance: 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 a single daily dose
• CrCl <15 mL/min: 100-300 mg/day as a single daily dose
• Hemodialysis patients: Maintenance dose based on CrCl plus supplemental 125-350 mg post-dialysis dose after each 4-hour session 1

Timeline for Therapeutic Trial

Allow a minimum of 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. 5, 2

• Efficacy for neuropathic pain develops gradually over several weeks 2
• If 1800 mg/day is ineffective after an adequate trial, increase to 3600 mg/day, as some patients require higher doses 5

Common Adverse Effects

Adverse events occur in 63% of gabapentin-treated patients versus 49% with placebo: 4

• Dizziness: 19% of patients 4
• Somnolence: 14% 4
• Peripheral edema: 7% 4
• Gait disturbance: 14% 4
• Withdrawal due to adverse events: 11% versus 8.2% with placebo 4

These effects are typically mild to moderate and often subside within approximately 10 days from initiation. 6, 7

Critical Pitfalls to Avoid

Do not rush titration in elderly patients, as this increases fall risk from dizziness. 2

Do not discontinue gabapentin abruptly—taper gradually over at least 1 week to avoid withdrawal symptoms. 2, 1

Do not use once-daily or twice-daily dosing for standard gabapentin, as three times daily administration is essential. 2

Do not abandon treatment prematurely—allow the full 2-month trial period before declaring failure. 2

Special Populations

Elderly patients: Start at the lower end of the dosing range (100 mg at bedtime) with slower titration every 3-7 days, and adjust dose based on creatinine clearance. 2, 1

Pediatric patients (3-11 years) with epilepsy: Starting dose 10-15 mg/kg/day in three divided doses, with maintenance doses of 25-50 mg/kg/day depending on age. 1