Gabapentin Prescribing Guidelines
Start gabapentin at 300 mg three times daily (or 300 mg at bedtime for cautious initiation) and titrate to 1800-3600 mg/day in divided doses for neuropathic pain, with the FDA-approved rapid titration protocol reaching 900 mg/day by day 3 for postherpetic neuralgia. 1
Indication-Specific Dosing
Postherpetic Neuralgia
- FDA-approved rapid titration: Day 1: 300 mg once, Day 2: 300 mg twice daily, Day 3: 300 mg three times daily (900 mg/day total) 1
- Target dose: 1800 mg/day (600 mg three times daily), which provides substantial pain relief (≥50% reduction) in 32% of patients versus 17% with placebo 2
- Maximum dose: 3600 mg/day, though additional benefit above 1800 mg/day has not been clearly demonstrated in clinical trials 1
Painful Diabetic Neuropathy
- Recommended dose range: 900-3600 mg/day in three divided doses 3
- Efficacy: At doses ≥1200 mg/day, 38% achieve substantial benefit (≥50% pain relief) versus 21% with placebo 2
- Position in therapy: Gabapentin is an established option alongside tricyclic antidepressants, though only duloxetine and pregabalin have FDA approval specifically for diabetic neuropathy 3
Partial Onset Seizures (Adults ≥12 years)
- Starting dose: 300 mg three times daily 1
- Maintenance dose: 300-600 mg three times daily 1
- Maximum dose: 2400 mg/day is well-tolerated long-term; 3600 mg/day has been used short-term in small numbers 1
- Dosing interval: Maximum 12 hours between doses 1
Titration Strategy
For neuropathic pain, an adequate trial requires 3-8 weeks for titration plus 2 weeks at maximum dose to properly evaluate efficacy. 4
Standard Titration Approach
- Start with 100-300 mg at bedtime OR 100-300 mg three times daily 4
- Increase gradually to 900-3600 mg/day in divided doses 4
- For most patients: Start 300 mg three times daily, titrate to 600 mg three times daily over 1-2 weeks 4
- Effective doses typically range from 1800-3600 mg/day for neuropathic pain 5
Special Populations
Elderly Patients
- Use lower starting doses and slower titration to minimize adverse effects 4, 1
- Dose selection should be based on creatinine clearance values 1
- Higher risk of dizziness, somnolence, peripheral edema, and falls 2
Renal Impairment
Dose adjustment is mandatory based on creatinine clearance: 1
| Creatinine Clearance | Total Daily Dose | Dosing Regimen |
|---|---|---|
| ≥60 mL/min | 900-3600 mg/day | 300-1200 mg TID |
| 30-59 mL/min | 400-1400 mg/day | 200-700 mg BID |
| 15-29 mL/min | 200-700 mg/day | 200-700 mg once daily |
| <15 mL/min | 100-300 mg/day | 100-300 mg once daily |
| Hemodialysis | Based on CLCr above | Plus 125-350 mg post-dialysis supplemental dose |
Efficacy Expectations
Realistic Outcomes
- 3-4 out of 10 patients achieve ≥50% pain relief with gabapentin versus 1-2 out of 10 with placebo 2
- Over half of treated patients will not have worthwhile pain relief but may experience adverse events 2
- Gabapentin relieves allodynia, burning pain, shooting pain, and hyperesthesia 5
Adverse Effects Profile
Common Side Effects (High-Quality Evidence)
- Dizziness: 19% of patients 2
- Somnolence: 14% of patients 2
- Peripheral edema: 7% of patients 2
- Gait disturbance: 14% of patients 2
- Any adverse event: 63% with gabapentin versus 49% with placebo 2
Withdrawal and Serious Events
- Adverse event withdrawals: 11% with gabapentin versus 8.2% with placebo (NNH 30) 2
- Serious adverse events: No significant difference from placebo (3.2% vs 2.8%) 2
- Most adverse effects are mild to moderate and typically subside within approximately 10 days 5
Critical Prescribing Pitfalls to Avoid
Do NOT:
- Start at high doses (e.g., 800 mg four times daily) without gradual titration—this dramatically increases adverse effects 4
- Exceed 3600 mg/day maximum dose 4, 1
- Use doses above 2400 mg/day without caution, especially in older adults 4
- Allow more than 12 hours between doses 1
- Abruptly discontinue—taper gradually over minimum 1 week (longer at prescriber discretion) 1
Do NOT use half-tablets beyond 28 days:
- If dividing scored 600 mg or 800 mg tablets, the unused half should be taken as the next dose 1
- Discard unused half-tablets after 28 days 1
Administration
- Can be taken with or without food 1
- Administer three times daily for most indications 1
- For patients with difficulty tolerating initial doses, starting at bedtime may improve tolerability 4, 5
Comparison with Pregabalin
- Pregabalin has more predictable absorption and linear pharmacokinetics compared to gabapentin 6
- Pregabalin maximum dose is 600 mg/day versus 3600 mg/day for gabapentin 6
- Both medications share similar adverse effect profiles including dizziness, somnolence, and peripheral edema 6
- Only duloxetine and pregabalin have FDA approval specifically for diabetic neuropathic pain, though gabapentin has proven efficacy 3