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 600 mg/day (300 mg twice daily) on day 2, then 900 mg/day (300 mg three times daily) on day 3, and titrate up to an effective dose of 1800-3600 mg/day divided into three doses. 1

Initial Titration Protocol

The FDA-approved initiation schedule provides the safest approach to minimize adverse effects while achieving therapeutic levels:

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

For elderly or medically frail patients, use slower titration with dose increments of 50-100% every few days rather than daily increases 3, 2

Target Therapeutic Dose Range

For Postherpetic Neuralgia

• Effective range: 1800-3600 mg/day divided into three doses 1
• The FDA label notes that efficacy was demonstrated across this dose range, but additional benefit above 1800 mg/day was not clearly demonstrated in clinical studies 1
• Most patients achieve adequate pain relief at 1800 mg/day (600 mg three times daily) 1, 4

For Painful Diabetic Neuropathy

• Effective range: 900-3600 mg/day divided into 2-3 doses 3, 2
• Clinical trials show 38% of patients achieve at least 50% pain reduction at doses of 1200 mg/day or greater 5
• Most patients require 1800-3600 mg/day for optimal pain relief 2

For Epilepsy (Partial Onset Seizures)

• Adults and children ≥12 years: Starting dose is 300 mg three times daily 1
• Maintenance dose: 300-600 mg three times daily 1
• Maximum studied dose: 2400 mg/day is well tolerated; doses up to 3600 mg/day have been used short-term 1

Administration Schedule

• Divide total daily dose into three administrations per day for optimal therapeutic effect 3, 2, 1
• Maximum time between doses should not exceed 12 hours 1
• Administer with or without food 1
• Due to nonlinear pharmacokinetics, three-times-daily dosing is necessary to maintain therapeutic levels 2

Dose Adjustments for Renal Impairment

Critical consideration: Gabapentin is eliminated unchanged by the kidneys, requiring dose adjustment for any degree of renal dysfunction 3, 1

FDA-Recommended Renal Dosing:

• CrCl ≥60 mL/min: 900-3600 mg/day in three divided doses 1
• CrCl 30-59 mL/min: 400-1400 mg/day in two divided doses 1
• CrCl 15-29 mL/min: 200-700 mg/day as single daily dose 1
• CrCl <15 mL/min: 100-300 mg/day as single daily dose 1
• Hemodialysis patients: Maintenance dose based on creatinine clearance plus supplemental post-dialysis dose of 125-350 mg after each 4-hour dialysis session 1

Duration of Adequate Trial

• Allow at least 3-8 weeks for titration plus 2 weeks at maximum tolerated dose before concluding treatment failure 2
• If 1800 mg/day is ineffective after adequate trial, increase to 3600 mg/day as some patients require higher doses 2
• Most clinical studies demonstrating efficacy were 4-12 weeks in duration 5

Common Adverse Effects and Management

The most frequent adverse effects that may require dose adjustment or discontinuation include:

• Dizziness: 19% of patients 5
• Somnolence: 14% of patients 5
• Peripheral edema: 7% of patients 5
• Gait disturbance: 14% of patients 5
• Adverse event withdrawals: 11% with gabapentin vs 8.2% with placebo 5

These effects can be minimized by starting with lower dosages and titrating cautiously 2

Discontinuation Protocol

When reducing, discontinuing, or substituting gabapentin, taper gradually over a minimum of 1 week (longer periods may be needed at prescriber's discretion) 1

Clinical Pearls

• Patient education should emphasize the trial-and-error nature of treatment to prevent discouragement during titration 3
• Response varies among different types of neuropathic pain and individual patients 3, 2
• Gabapentin may be used as coanalgesic in combination with opioids for the neuropathic component of pain 3
• If gabapentin is not tolerated, consider pregabalin, which has similar efficacy but linear pharmacokinetics and simpler dosing (50 mg three times daily or 75 mg twice daily, titrated to 300-600 mg/day) 2
• Doses should be increased until analgesic effect is achieved, side effects become unmanageable, or the conventional maximum dose (3600 mg/day) is reached 3