What is the recommended dose of gabapentin (Neurontin) for adults with neuropathic pain or epilepsy, especially in patients with impaired renal function?

Gabapentin Dosing for Neuropathic Pain and Epilepsy

Start gabapentin at 300 mg on day 1, increase to 600 mg/day (300 mg twice daily) on day 2, and 900 mg/day (300 mg three times daily) on day 3, then titrate to a target dose of 1800 mg/day (600 mg three times daily) for neuropathic pain, with a maximum of 3600 mg/day if needed. 1

Standard Dosing Protocol for Neuropathic Pain

Initial Titration:

• Day 1: 300 mg once daily (at bedtime preferred) 1, 2
• Day 2: 600 mg/day (300 mg twice daily) 1
• Day 3: 900 mg/day (300 mg three times daily) 1
• Continue increasing by 300 mg every 1-7 days as tolerated 2, 3

Target Therapeutic Dose:

• Minimum effective dose: 1800 mg/day (600 mg three times daily) 2, 1
• Standard range: 1800-3600 mg/day in three divided doses 2, 4
• Maximum dose: 3600 mg/day (1200 mg three times daily) 1, 5

The FDA label confirms that in clinical studies for postherpetic neuralgia, efficacy was demonstrated across 1800-3600 mg/day, though additional benefit above 1800 mg/day was not consistently demonstrated 1. However, some patients do require higher doses up to 3600 mg/day for optimal pain relief 5, 4.

Critical Dosing Considerations

Three-Times-Daily Dosing is Mandatory:

• Gabapentin has nonlinear, saturable absorption that becomes less efficient at higher doses 2
• The maximum interval between doses should not exceed 12 hours 1
• Once-daily or twice-daily dosing is inadequate for standard gabapentin formulations 2

Adequate Trial Duration:

• Allow 3-8 weeks for titration plus 2 weeks at maximum tolerated dose 2
• An adequate trial may require 2 months or more before declaring treatment failure 2
• Efficacy develops gradually over several weeks 6

Dosing for Epilepsy (Partial Onset Seizures)

Adults and Children ≥12 years:

• Starting dose: 300 mg three times daily 1
• Maintenance dose: 300-600 mg three times daily 1
• Maximum studied dose: 2400 mg/day (well tolerated in long-term studies); 3600 mg/day administered to small numbers for short duration 1

Pediatric Patients (3-11 years):

• Starting dose: 10-15 mg/kg/day in three divided doses 1
• Ages 3-4 years: Target 40 mg/kg/day in three divided doses 1
• Ages 5-11 years: Target 25-35 mg/kg/day in three divided doses 1
• Doses up to 50 mg/kg/day have been well tolerated 1

Renal Impairment Dosing (Critical Adjustment Required)

Gabapentin is eliminated unchanged by the kidneys, requiring mandatory dose reduction based on creatinine clearance 1, 2:

• CrCl ≥60 mL/min: 900-3600 mg/day (300-1200 mg three times daily) 1
• CrCl 30-59 mL/min: 400-1400 mg/day (200-700 mg twice daily) 1
• CrCl 15-29 mL/min: 200-700 mg/day (200-700 mg once daily) 1
• CrCl <15 mL/min: 100-300 mg/day (100-300 mg once daily) 1

Hemodialysis Patients:

• Base maintenance dose on creatinine clearance as above 1
• Administer supplemental post-hemodialysis dose of 125-350 mg after each 4-hour dialysis session 1

Special Population Considerations

Elderly Patients:

• Start at the lowest doses (100-200 mg/day) 6
• Use slower titration with increases every 3-7 days 6, 2
• Adjust dose based on creatinine clearance, as elderly patients are more likely to have decreased renal function 1
• The effective dose in older adults may be lower than standard ranges 6

Common Pitfall: Elderly patients are particularly vulnerable to side effects including somnolence, dizziness, mental clouding, falls, and confusion 6. Starting with low doses and slow titration is essential to minimize these risks.

Expected Efficacy

Postherpetic Neuralgia:

• 34% achieve at least 50% pain reduction with gabapentin versus 21% with placebo (NNT 8.0) 4
• 46% achieve at least 30% pain reduction versus 25% with placebo (NNT 4.8) 4

Painful Diabetic Neuropathy:

• 38% achieve at least 50% pain reduction versus 21% with placebo (NNT 5.9) 4
• 52% achieve at least 30% pain reduction versus 37% with placebo (NNT 6.6) 4

Adverse Effects Profile

Common Side Effects (dose-dependent):

• Dizziness (19%) 4
• Somnolence (14%) 4
• Peripheral edema (7%) 4
• Gait disturbance (14%) 4

These are typically mild to moderate and often transient, usually subsiding within approximately 10 days from initiation 5. Adverse event withdrawals occur in 11% versus 8.2% with placebo (NNH 30) 4.

Discontinuation Protocol

Never discontinue abruptly - taper gradually over a minimum of 1 week (longer periods may be needed at prescriber's discretion) to avoid withdrawal symptoms 1, 2.

Clinical Pearls

• Gabapentin is a first-line therapy for chronic neuropathic pain, particularly postherpetic neuralgia and painful diabetic neuropathy 6
• Patients may respond to gabapentin, pregabalin, both, or neither - individual response varies 6
• If gabapentin at 1800 mg/day is ineffective after an adequate trial, consider increasing to 3600 mg/day before switching agents 3
• Gabapentin has minimal drug interactions and a favorable safety profile 2
• Can be used as a coanalgesic in combination with opioids, antidepressants, or topical agents 3