What is the recommended use and dosing of Gabapentin (Neurontin) for treating neuropathic pain and epilepsy?

Gabapentin for Neuropathic Pain and Epilepsy

Start gabapentin at 300 mg once daily or at bedtime, titrate to 300 mg three times daily by day 3, then increase by 300 mg every 3-7 days until reaching the target therapeutic dose of 1800-3600 mg/day in three divided doses for neuropathic pain. 1, 2

Initial Dosing and Titration Strategy

Standard Adult Dosing

• Day 1: 300 mg once daily (at bedtime or with evening meal) 2
• Day 2: 300 mg twice daily (600 mg/day total) 2
• Day 3: 300 mg three times daily (900 mg/day total) 2
• Days 4-21: Increase by 300 mg every 3-7 days as tolerated 1, 2

Target Therapeutic Doses

• Minimum effective dose: 1800 mg/day (600 mg three times daily) for most neuropathic pain conditions 1, 2
• Maximum dose: 3600 mg/day (1200 mg three times daily) for optimal pain relief 1, 2
• Three-times-daily dosing is mandatory due to saturable, nonlinear absorption pharmacokinetics—once or twice daily dosing is inadequate 1, 3

Condition-Specific Dosing

Postherpetic Neuralgia

• Effective dose range: 1800-3600 mg/day in three divided doses 4, 2
• 32% of patients achieve at least 50% pain reduction at doses ≥1200 mg/day versus 17% with placebo (NNT 6.7) 5
• 46% achieve at least 30% pain reduction versus 25% with placebo (NNT 4.8) 5

Diabetic Peripheral Neuropathy

• Effective dose range: 1800-3600 mg/day in three divided doses 4, 1
• 38% of patients achieve at least 50% pain reduction at doses ≥1200 mg/day versus 21% with placebo (NNT 5.9) 5
• Doses up to 3600 mg/day have been well tolerated in clinical trials 4

HIV-Associated Neuropathic Pain

• Titrate to maximum of 2400 mg/day over 4 weeks in divided doses 4, 1
• Gabapentin is strongly recommended as first-line oral pharmacological treatment by the Infectious Diseases Society of America 4, 1

Epilepsy with Partial Onset Seizures

• Adults and children ≥12 years: Starting dose 300 mg three times daily, with maintenance dose of 300-600 mg three times daily 2
• Dosages up to 2400 mg/day have been well tolerated in long-term studies 2
• Children 3-11 years: Starting dose 10-15 mg/kg/day in three divided doses, with maintenance dose of 25-35 mg/kg/day (ages 5-11) or 40 mg/kg/day (ages 3-4) 2

Special Population Considerations

Elderly or Medically Frail Patients

• Start at 100 mg at bedtime and increase by 100-300 mg every 3-7 days (slower titration) 1, 3
• Mandatory dose adjustment based on creatinine clearance due to age-related renal decline 1, 2
• Critical pitfall: Rushing titration increases fall risk from dizziness 1

Renal Impairment Dosing

Mandatory dose reduction based on creatinine clearance 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 patients: Maintenance dose based on CrCl plus supplemental post-dialysis dose of 125-350 mg after each 4-hour session 2

Timeline for Efficacy Assessment

• Minimum trial duration: 3-8 weeks for titration plus 2 weeks at maximum tolerated dose 1
• Adequate therapeutic trial: Potentially requires 2 months or more before declaring treatment failure 1
• Efficacy for neuropathic pain develops gradually over several weeks 1

Adverse Effects and Safety

Common Side Effects

• Dizziness (19%), somnolence (14%), peripheral edema (7%), and gait disturbance (14%) 5
• Adverse effects are typically mild to moderate and often transient, usually subsiding within approximately 10 days 4, 6
• 80% of patients reported somnolence at 2400 mg/day in HIV neuropathy trials 4

Withdrawal Rates

• Adverse event withdrawals: 11% with gabapentin versus 8.2% with placebo (NNH 30) 5
• Serious adverse events: 3.2% with gabapentin versus 2.8% with placebo (no significant difference) 5

Critical Pitfalls to Avoid

• Never use once-daily or twice-daily dosing for standard gabapentin—three times daily administration is essential due to saturable absorption 1
• Never discontinue abruptly—taper gradually over at least 1 week to avoid withdrawal symptoms 1, 2
• Never rush titration in elderly patients—increases fall risk from dizziness 1
• Never exceed 12 hours between doses to maintain therapeutic levels 2
• Allow the full 2-month trial period before declaring treatment failure, as efficacy develops gradually 1

Gabapentin vs. Pregabalin

• Gabapentin has nonlinear pharmacokinetics making dose titration less predictable, while pregabalin has linear pharmacokinetics 1, 3
• Generic gabapentin is typically less expensive than pregabalin 3
• Gabapentin is recommended as first-line treatment for HIV-associated neuropathic pain, with pregabalin considered only after inadequate response 3
• Both medications bind to the α2δ subunit of voltage-gated calcium channels, reducing neurotransmitter release 4, 3

Administration Pearls

• Administer with or without food 2
• If dividing scored 600 mg or 800 mg tablets, take unused half-tablet as next dose within 28 days 2
• Gabapentin has minimal drug interactions and a favorable safety profile 1
• May be used as coanalgesic in combination with opioids, antidepressants, or topical agents 1